2,2,2-trifluoro-N-((1S,3R)-3-hydroxy-6-isopropoxy-2,3-dihydro-1H-inden-1-yl)acetamide → (S)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoate

HRID 501744Notes

Reaction equation

HRID 501744 reaction equation
FC(F)(F)C(N[C@@H]1C2C(=CC=C(OC(C)C)C=2)[C@H](O)C1)=O.[CH2:22]([O:29][C:30]([NH:32]/[C:33](=[CH:38]\[C:39]1[CH:44]=[C:43]([Cl:45])[CH:42]=[C:41]([Cl:46])[CH:40]=1)/[C:34]([O:36][CH3:37])=[O:35])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:22]([O:29][C:30]([NH:32][C@@H:33]([CH2:38][C:39]1[CH:40]=[C:41]([Cl:46])[CH:42]=[C:43]([Cl:45])[CH:44]=1)[C:34]([O:36][CH3:37])=[O:35])=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 594236882,2,2-trifluoro-N-((1S,3R)-3-hydroxy-6-isopropoxy-2,3-dihydro-1H-inden-1-yl)acetamideHCID 68461432(Z)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)acrylate

Product 1

HCID 68464283(S)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoateYield 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step BF (2): To a solution of (Z)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)acrylate (46.08 g, 121.3 mmol) in methylene chloride (435 mL) was added (+)-1,2-bis((2S,5S)-2,5-Diethylphospholano)benzene(cyclooctadiene)Rhodium(I) trifluoromethanesulfonate (4.02 g, 6.08 mmol). The solution was split between two Parr bottles and shaken under 50 psi hydrogen for 8 h. The combined reactions were concentrated in vacuo and subjected to silica gel chromatography (25% EtOAc/hexane) to yield (S)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)propanoate (40.94 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ 7.28-7.39 (m, 5H) 7.24 (d, J=7.02 Hz, 1H) 7.00 (s, J=1.53 Hz, 2H) 5.34 (d, J=7.63 Hz, 1H) 5.10 (q, J=12.21 Hz, 2H) 4.58-4.68 (m, 1H) 3.73 (s, 3H) 3.05-3.15 (m, 1H) 2.95-3.05 (m, 1H).

Workup

  1. customThe solution was split between two Parr bottles
  2. concentrationThe combined reactions were concentrated in vacuo

Sources & evidence

ORD record
ord-af3617cdb4a74e76a4cde6c7f22479fe
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…