目錄
一、加料過程常用表述
1. 添加試劑
2. 催化量的
3. 氣體保護
4. 通入氣體
5. 通過雙針頭導管加料
6. 通過注射器加料
二、反應過程常用表述
1. 反應檢測
2. 放置過夜
3. 甲苯/乙醇帶水
4. 氫化反應
5. 分水器
6. 反應放熱
7. 微波反應
三、後處理過程常用表述
1. 過濾
2. 淬火
3. 磨碎
4. 在兩相中分開
5. 靜止固化
6. 在凍幹機凍幹
7. 純化
過柱
製備HPLC純化
製備TLC純化
重結晶
8. 調pH
9. 萃取
10. 濃縮
11. 乾燥
乾燥
真空乾燥
四、部分常見反應現象描述
1. 加料放熱
2. 反應過程中或者降溫有固體析出
3. 加料不溶解
4. 加熱溶解
5. 反應變粘稠/變色
五、特殊結果敘述
1. 無進一步處理
2. 統一和其他批次一起後處理
3. 檢測條件，不需要後處理
六、一些易錯寫法
一、加料過程常用表述1. 添加試劑To a mixture (suspension / solution / slurry) ofcompound 12 (487 mg, 1 mmol) and o-plenylenediamine (648 mg, 6 mmol) inCH2Cl2(15 mL) being cooled to 0oC was addedthe DCC (226 mg, 1.1 mmol).
Anhydrous lithium iodide (1.38 g, 10.3 mmol) was added the five portions (dropwise/ in one portion / in portions) to a stirred solution of compound 12 (10.93 g, 51.5mmol) in CH2Cl2(120 mL).
A round-bottom flask was charged with compound 3 (1.75 g, 5.27 mmol), LiCl (1.17 g, 26.3 mmol), DMSO (100 mL) and H2O (378ul)
2. 催化量的
Et3N (20 mL, 142 mmol) and a catalytic amount of DMAP were added the solution of compound 1 (4.549 g, 46.4mmol) in CH2Cl2(120 mL) at 0oC
3.氣體保護
To a stirred -78oC solution of trimethylsilyacetylene (4.44 g, 45.5 mmol) in THF (10 mL) under Argon wasadded dropwise n-butylithium (1.6 M in hexane, 28.25 mL).
4. 通入氣體
An ozone-enriched steam of oxygen was bubbled througha cold (-78oC) solution of compound 9 (128 mg, 1.409 mmol) in CH2Cl2 (5 mL) untilit turned light blue. The solution was purged with argon at -78oCfor 10 min to remove the excess O3.
5. 通過雙針頭導管加料
The mixture was added to a solution of compound 2 (3.00 g, 12.8 mmol) in THF (48mL) via cannula over a period of 30 min.
A solution of compound 29 (100 mg, 0.19 mmol, 1.0 equiv) in dry DMSO (1.5 mL) wascannulated under Argon to a vigorously stirred mixture of powered potassiumsuperoxide (62 mg, 0.87 mmol, 4.5 equiv) and 18-crown-6-ether (23 mg, 0.087mmol, 0.45 equiv) in dry DMSO (0.5 mL).
6. 通過注射器加料
To a stirred solution of compound 15 (8.61 g, 21.2 mmol)was added a solution of p-toluenesulfonicacid (6.0 g) in CH2Cl2via syringe over 5 min.
二、反應過程常用表述1. 反應檢測
After 1 h, TLC analysis (CH2Cl2/ hexane 3:1) showed the complete consumption of compound 15.
2. 放置過夜
The mixture was left standing overnight.
3. 甲苯/乙醇帶水
Compound A(1.97 g, 6.63 mmol) was coevaporated with toluene five times to remove the water. The residue was subjected to toluene azeotrope to givethe corresponding acid chloride as brown oil. The aqueous portion was concentrated underreduced pressure followed by azeotropic removal of water with absolute EtOH
4. 氫化反應
A mixture of compound 1 (190 g, 0.88mmol) and Raney Ni (20 g) inethanol (1500 mL) and ethyl acetate (500 mL) was stirred under 1 atm at room temperaturefor an hour.
5. 分水器
A mixture of TsOH.H2O (56.91 g, 0.3 mol) and toluene (400 mL) was heated to reflux to remove water by Dean-Stark trap.
6. 反應放熱
The reaction was exothermic.
7. 微波反應
The sealed vial was irradiated in the microwave on a Biotage Smith Synthesis at 150oC for 10 min.
三、後處理過程常用表述1. 過濾
The mixture was filtered through a Celite pad, and thefiltrate was concentrated to give the crude product.
2. 淬滅The reaction mixture was quenched by the addition of thesaturated aqueous NH4Cl.
3. 磨碎The residue was triturated with ether and filtered to afforda white solid.
4. 在兩相中分開The residue was partitioned between ethyl acetate (100mL) and HCl (1 M aq., 50mL). The organic layer was washed with water, dried (MgSO4) andevaporated to dryness. Ethyl acetate (100 mL) and HCl (1 M aq., 50 mL) were added to the residue,and the layers were separated.
5. 靜止固化
The crude product was purified by prep-HPLC to givecompound 4as colorless thick oil,which was solidified on standing.
6. 在凍幹機凍幹
The white solid was re-crystallized from water, driedby hyophilization to give a white solid.
7. 純化過柱：The crude product was chromatographed on silica gel(CH2Cl2 / MeOH 20:1→10:1→5:1) to give the compound 8 (0.282 g,51%) as a white solid. The crude product was purified by column chromatographyon silica gel eluted with (CH2Cl2 / MeOH，20:1→10:1→5:1) to give the compound 8 (0.282 g, 51%) as a white solid.
製備HPLC純化
be purified by prep-HPLC to afford/give/yield
製備TLC純化
be purified by prepare TLC to afford/give/yield
重結晶
recrystallized from
8. 調 pHThe pH was adjusted to around 9 by progressivelyadding solid NaHCO3
The mixture was adjusted to pH 9 with solid NaHCO3
9. 萃取
The aqueous layer was extracted with ethyl acetate (100mL × 4).
10. 濃縮
The mixture was evaporated to afford the crudeproduct.
The mixture was concentrated afford the crude product.
The solvent was removed to afford the crude product.
11. 乾燥乾燥：The organic layer was dried over MgSO4, andconcentrated.
真空乾燥：The precipitate was filtered and dried in vacuo (in/ undervacumm; under reduced pressure).
四、部分常見反應現象描述1. 加料放熱
A gentle reflux appeared throughout the addition
Heat generated during the addition.
The temperature was increased from 25oC to50oC during the addition.
2. 反應過程中或者降溫有固體析出
Solid was precipitate out after 1h reaction.
The reaction mixture was cooled to -10oC,and solid was precipitate out.
3. 加料不溶解
XX was added to the mixture, and the resultingsuspension was stirred for 2hrs.
4. 加熱溶解
The suspension was heated to 90oC andstirred until all solid was dissolved.
5. 反應變粘稠/變色
The reaction mixture became sticky after 2hrsreaction/stirring.
After 2hrs stirring, the mixture turned intoblack/brown/gray/yellow/red color.
五、特殊結果敘述1. 無進一步處理
No further operation
2. 統一和其他批次一起後處理
The work-up of this batch was together with the otherbatches that recorded in the following pages.
3. 檢測條件，不需要後處理
IPC check showed this condition is better/bad for thisreaction. No further operation forcondition screen reaction.
六、一些易錯寫法
Right（正確）
Wrong（錯誤）
pH
PH
m-CPBA
MCPBA
1HNMR
HNMR
mL
ml