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

HRID 388871노트

반응식

HRID 388871 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-65574beac96445c48d0ccc35920cff22
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08377978B2

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