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

HRID 1844800Notes

Reaction equation

[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

Participants

Conditions

Temperature: 25 °C

Procedure

To a suspension of (E)-(R)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid [2(ii-a)] (20 g, 52 mmol) in degassed ethanol (100 ml) is added a solution of diiodo(p-cymene)ruthenium(II) dimer (0.215 g, 0.22 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) (0.50 g, 0.47 mmol) in degassed ethanol (15 ml). The solution is degassed using vacuum and a pressure of 20 bar hydrogen is applied. The mixture is stirred at 25° C. for 15 h. The vessel is then purged with nitrogen. The solvent is removed in vacuo. The resulting solid is dried overnight at 50° C. under 1-50 mbar vacuum to afford the title compound [Ratio 2(i-a): 2(i-b) 7:93, as determined by HPLC analysis].

Workup

customThe solution is degassed
customThe vessel is then purged with nitrogen
customThe solvent is removed in vacuo
customThe resulting solid is dried overnight at 50° C. under 1-50 mbar vacuum

Sources & evidence

ORD record: ord-89ecb5ea21a64d57a95e6e0e89491b26
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946481B2

Reaction notes

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