Benzyl Bromide → (S)-2-amino-3-(3'-chloro-biphenyl-4-yl)-propionic acid benzyl ester

HRID 388871ノート

反応式

HRID 388871 の反応式
C(OC([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=O)(C)(C)C.[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[CH2:27]([O:12][C:10](=[O:11])[C@@H:9]([NH2:8])[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)=[CH:18][CH:19]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

参加物

6

反応物 3

HCID 7498Benzyl BromideHCID 516892Sodium BicarbonateHCID 58280562(S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acid

生成物 1

HCID 58280537(S)-2-amino-3-(3'-chloro-biphenyl-4-yl)-propionic acid benzyl ester収率 89.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (S)-2-tert-butoxycarbonylamino-3-(3′-chloro-biphenyl-4-yl)-propionic acid (12.9 g, 34.3 mmol) in DMF (130 mL) were added benzyl bromide (8.16 mL, 68.6 mmol) and NaHCO3 (5.77 g, 68.6 mmol). After stirred at room temperature overnight, the reaction mixture was diluted with EtOAc. The mixture was washed with H2O and brine, dried over Na2SO4, and concentrated under reduced pressure. The obtained residue was treated with 4M HCl in dioxane (30 mL) and stirred for 2 hours. The reaction mixture was concentrated and the resulted residue was rinsed with iPr2O to give (S)-2-amino-3-(3′-chloro-biphenyl-4-yl)-propionic acid benzyl ester (11.2 g). 1H NMR (400 MHz, DMSO-d6) δ 3.14 (dd, 1H, J=7.7, 12.0 Hz), 3.27 (dd, 1H, J=5.9, 12.0 Hz), 4.38 (dd, 1H, J=5.9, 7.7 Hz), 5.15 (s, 2H), 7.23-7.27 (m, 2H), 7.30-7.34 (m, 5H), 7.42-7.45 (m, 1H), 7.51 (dd, 1H, J=7.6, 7.6 Hz), 7.61-7.66 (m, 3H), 7.69 (dd, 1H, J=1.8, 1.8 Hz), 8.64 (bs, 2H); MS: m/z (MH+) 366.

後処理

  1. washThe mixture was washed with H2O and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionThe obtained residue was treated with 4M HCl in dioxane (30 mL)
  5. stirringstirred for 2 hours
  6. concentrationThe reaction mixture was concentrated
  7. washthe resulted residue was rinsed with iPr2O

出典と根拠

ORDレコード
ord-65574beac96445c48d0ccc35920cff22
出典データセット
uspto-grants-2013_02
特許番号
US08377978B2

反応ノート

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