(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 1844799ノート

反応式

HRID 1844799 の反応式
[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

参加物

4

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 10920157HCID 10920157、化合物触媒HCID 702Ethanol溶媒2 回

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c58a711508a742f1a8f7ace4a0d4207c
出典データセット
uspto-grants-2015_02
特許番号
US08946481B2

反応ノート

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