(2E,4R)-5-(1,1'-Biphenyl)-4-yl-4-(((1,1-dimethylethoxy)carbonyl)amino)-2-methyl-2-pentenoic acid → (2S,4S)-5-([1,1'-Biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid

HRID 1844799노트

반응식

HRID 1844799 반응식
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])/[CH:9]=[C:10](\[CH3:14])/[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1>C(O)C.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.[Ru](I)I.[Ru](I)I>[C:1]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:9][C@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:5][CH:6]=1

참가 물질

4

반응물 1

HCID 56846981(2E,4R)-5-(1,1'-Biphenyl)-4-yl-4-(((1,1-dimethylethoxy)carbonyl)amino)-2-methyl-2-pentenoic acid

생성물 1

HCID 46193547(2S,4S)-5-([1,1'-Biphenyl]-4-yl)-4-((tert-butoxycarbonyl)amino)-2-methylpentanoic acid

시약·촉매·용매 2

HCID 10920157HCID 10920157, 화합물촉매HCID 702Ethanol용매2회

반응 조건

온도
60 °C

실험 절차

To a suspension of (E)-(R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid [2(ii-a)] (10 g, 26.1 mmol) in degassed ethanol (90 ml) is added a solution of diiodo(p-cymene)ruthenium(II) dimer (0.156 g, 0.16 mmol) and (αS,αS)-2,2′-bis(α-N,N-dimethylaminophenylmethyl)-(R,R)-1,1′-bis[di(3,5-dimethyl-4-methoxyphenyl)phosphine]ferrocene (=Mandyphos SL-M004-2) (0.348 g, 0.33 mmol) in degassed ethanol (30 ml) portion wise over the entire reaction time of 5 days. The solution is degassed using vacuum and a pressure of 5.5 bar hydrogen is applied. The mixture is heated to 60° C. and stirred at this temperature for 5 days. The vessel is then purged with nitrogen. The solvent is removed in vacuo. The resulting solid is dissolved in isopropyl acetate (34 ml) and heated to reflux. An heptane fraction (68 ml) is added and the mixture is cooled to room temperature. The solid is collected by filtration and washed with an heptane-isopropyl acetate 2:1 mixture (20 ml). The solid is dried overnight at 50° C. under 1-50 mbar vacuum to afford the title compound [Ratio 2(i-a): 2(i-b) 6:94, as determined by HPLC analysis] as a grey solid. δH (500 MHz; DMSO) 1.06 (3H, d, J 7.0, 1-CH3), 1.32 (9H, s, (CH3)3), 1.42 (1H, m, 3-HA), 1.78 (1H, m, 3-HB), 2.39 (1H, m, 2-H), 2.73 (2H, d, J 7.0, 5-H), 3.73 (1H, m, 4-H), 6.75 (1H, d, J 9.5, NH), 7.29 (2H, d, J 8.0, Ar-ortho-H(Ph)), 7.35 (1H, t, J 7.0, Ar-(Ph)-para-H), 7.46 (2H, t, J 7.5, Ar-(Ph)-meta-H), 7.57 (2H, d, J 8.0, Ar-meta-H(Ph), 7.64 (2H, d, J 7.5, Ar-(Ph)-ortho-H), 12.01 (1H, s, CO2H); δC (500 MHz, DMSO) 16.2 (1-CH3), 28.2 [(CH3)3], 35.7 (2-C), 37.9 (3-C), 40.7 (5-C), 49.2 (4-C), 77.4 [(C(CH3)3], 126.3, 126.5, 127.2, 128.9, 129.7 (Ar—CH), 137.8 (Ar-ipso-C(Ph)), 138.4 (Ar-para-C(Ph)), 140.1 (Ar-(Ph)-ipso-C), 155.3 (NCO), 177.6 (CO2H); m/z (+ESI) 406 ([MNa]+, 4%), 384 ([MH]+, 44), 328 (100), 284 (22); Found: [MH]+, 384.21696. C23H30NO4 requires MH 384.21693.

후처리

  1. customThe solution is degassed
  2. customThe vessel is then purged with nitrogen
  3. customThe solvent is removed in vacuo
  4. dissolutionThe resulting solid is dissolved in isopropyl acetate (34 ml)
  5. temperatureheated to reflux
  6. additionAn heptane fraction (68 ml) is added
  7. temperaturethe mixture is cooled to room temperature
  8. filtrationThe solid is collected by filtration
  9. washwashed with an heptane-isopropyl acetate 2:1 mixture (20 ml)
  10. customThe solid is dried overnight at 50° C. under 1-50 mbar vacuum

출처 및 근거

ORD 기록
ord-c58a711508a742f1a8f7ace4a0d4207c
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946481B2

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