Potassium Carbonate → 3-(Dipropylcarbamoyl)benzoic acid

HRID 1014868

反応式

HRID 1014868 の反応式
F[C:2]1[CH:3]=C(C=C(F)[CH:27]=1)C[C@@H]([C@@H](C1COCCN1C(OC(C)(C)C)=O)O)C(O)=O.[Si](O[C@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)[C@@H:38]([NH:48][C:49](=[O:61])[C:50]1[CH:55]=[C:54](C)[CH:53]=[C:52]([C:57]([O:59]C)=[O:58])[CH:51]=1)[CH2:39][C:40]1C=C(F)C=C(F)C=1)(C(C)(C)C)(C)C.BrC1C=C(C=C(C(OC)=O)C=1)C(N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)O[Si](C(C)(C)C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH2:27]([N:48]([CH2:38][CH2:39][CH3:40])[C:49]([C:50]1[CH:51]=[C:52]([CH:53]=[CH:54][CH:55]=1)[C:57]([OH:59])=[O:58])=[O:61])[CH2:2][CH3:3]

参加物

9

反応物 5

HCID 11430Potassium CarbonateHCID 574072Trimethylboroxine3 回HCID 67315749(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylateHCID 67315777(2S,3S)-2-(3,5-difluorobenzyl)-3-(4-(tert-butoxycarbonyl)morpholin-3-yl)-3-hydroxypropanoic acidHCID 67316204(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-(methoxycarbonyl)-5-methylbenzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

生成物 1

HCID 1827693-(Dipropylcarbamoyl)benzoic acid収率 77%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

Step G (4): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-(methoxycarbonyl)-5-methylbenzamido)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate (Step G (3). 163 mg, 0.21 mmol) in DMF (10 mL) were added potassium carbonate (87 mg, 0.63 mmol), Pd(PPh3)4 (24 mg, 0.021 mmol), and trimethylboroxine (53 mg, 0.42 mmol) and the reaction mixture was stirred at 100° C. with sealed cap for 5 h. Then another portion of trimethylboroxine (53 mg, 0.42 mmol) was added and the reaction was stirred at 60° C. overnight. Another portion of trimethylboroxine (53 mg, 0.42 mmol) was added and the reaction was stirred at 100° C. for 6 h. Ethyl acetate (100 mL) was added and the mixture was washed with H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 5% to 10% to 15% EtOAc/Hexane step gradient) to give 110 mg of the title compound (77% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 0.02 (3H, s), 0.07 (3H, s), 0.85 (9H, s), 0.88 (3H, m), 1.45-1.52 (11H, m), 2.02-2.07 (1H, m), 2.20 (1H, d, J=15 Hz), 2.41 (3H, s), 2.66 (1H, dd, J=10, 15 Hz), 2.94 (1H, m), 3.28-3.37 (3H, m), 3.76 (1H, dd, J=5, 10 Hz), 3.90 (3H, s), 3.99 (1H, m), 4.07-4.13 (2H, m), 4.62 (1H, m), 6.59 (1H, m), 6.77 (1H, s), 6.79 (1H, s), 7.91 (1H, s), 7.94 (1H, s), 8.20 (1H, brd s), 8.34 (1H, s). MS (ESI) (M+H)+ 705.41.

後処理

  1. customwith sealed
  2. customcap for 5 h
  3. stirringthe reaction was stirred at 60° C. overnight
  4. stirringthe reaction was stirred at 100° C. for 6 h
  5. washthe mixture was washed with H2O
  6. concentrationconcentrated under vacuum
  7. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 5% to 10% to 15% EtOAc/Hexane step gradient)

出典と根拠

ORDレコード
ord-fd2a66bda81042b2acdbcb7b4a292529
出典データセット
uspto-grants-2011_07
特許番号
US07981913B2

関連ノート

読み込み中…