(S)-3-(3'-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl ester → (S)-3-(3'-Chloro-[1,1'-biphenyl]-4-yl)-2-(((S)-1-ethoxy-1-oxopropan-2-yl)amino)propanoic acid

HRID 388873노트

반응식

HRID 388873 반응식
C([O:8][C:9](=[O:33])[C@@H:10]([NH:25][C@H:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:27])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)=[CH:14][CH:13]=1)C1C=CC=CC=1>CCOC(C)=O.CO.[Pd]>[Cl:24][C:20]1[CH:19]=[C:18]([C:15]2[CH:14]=[CH:13][C:12]([CH2:11][C@H:10]([NH:25][C@H:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:27])[C:9]([OH:33])=[O:8])=[CH:17][CH:16]=2)[CH:23]=[CH:22][CH:21]=1

참가 물질

5

반응물 1

HCID 58280560(S)-3-(3'-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl ester

생성물 1

HCID 58280516(S)-3-(3'-Chloro-[1,1'-biphenyl]-4-yl)-2-(((S)-1-ethoxy-1-oxopropan-2-yl)amino)propanoic acid수율 69.3%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 887Methanol용매HCID 8857Ethyl Acetate용매

반응 조건

온도
12.5 °C

실험 절차

A suspension of (S)-3-(3′-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl ester (10.0 g, 21.5 mmol) and 5% Pd on carbon (0.914 g) in EtOAc (200 mL) was treated with H2 (balloon) and stirred at 10-15° C. for 1.5 hour and at room temperature for 0.5 hour. The resulted precipitate was dissolved in methanol and filtered through celite pad. The filtrate was concentrated under reduced pressure and the obtained residue was re-crystallized from EtOAc to give (S)-3-(3′-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid (5.6 g). The mother liquor was concentrated under reduced pressure and purified by silica gel column chromatography to give additional amount of (S)-3-(3′-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid (1.4 g). 1H NMR (400 MHz, DMSO-d6) δ 1.13 (t, 3H, J=7.1 Hz), 1.15 (d, 3H, J=6.8 Hz), 2.85 (dd, 1H, J=7.1, 14.1 Hz), 2.93 (dd, 1H, J=6.3, 13.6 Hz), 3.30-3.37 (m, 1H), 3.48 (dd, 1H, J=6.5, 6.5 Hz), 4.03 (q, 2H, J=7.1 Hz), 7.32 (d, 2H, J=8.3 Hz), 7.38-7.43 (m, 1H), 7.48 (dd, 1H, J=7.8, 7.8 Hz), 7.59-7.65 (m, 3H), 7.70 (dd, 1H, J=2.0, 2.0 Hz); MS: m/z (MH+) 376.

후처리

  1. additionwas treated with H2 (balloon)
  2. filtrationfiltered through celite pad
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe obtained residue was re-crystallized from EtOAc

출처 및 근거

ORD 기록
ord-1fd58a0175534860ac07733f53e278e7
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08377978B2

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