benzyl 2-(5-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate → 2-(5-(4'-(2-Methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetic acid

HRID 515392Notes

Reaction equation

HRID 515392 reaction equation
[CH3:1][C:2]1[O:3][C:4]([C:39]([F:42])([F:41])[F:40])=[C:5]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]4[CH2:27][O:26][CH:25]([CH2:28][C:29]([O:31]CC5C=CC=CC=5)=[O:30])[CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[CH:12][CH:11]=2)=[O:8])[N:6]=1>CCOC(C)=O.[OH-].[OH-].[Pd+2]>[CH3:1][C:2]1[O:3][C:4]([C:39]([F:42])([F:40])[F:41])=[C:5]([C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH:22]4[CH2:27][O:26][CH:25]([CH2:28][C:29]([OH:31])=[O:30])[CH2:24][CH2:23]4)=[CH:20][CH:21]=3)=[CH:14][CH:15]=2)=[O:8])[N:6]=1

Participants

4

Reactant 1

HCID 89872728benzyl 2-(5-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate

Product 1

HCID 721949032-(5-(4'-(2-Methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetic acidYield 80%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 9942167Palladium hydroxideSolvent

Procedure

Benzyl 2-(5-(4′-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1′-biphenyl]-4-yl)tetrahydro-2H-pyran-2-yl)acetate was dissolved in EtOAc and hydrogenated with 10% Pd(OH)2/C under H2 balloon for 30 min. The reaction mixture was filtered off to remove the catalyst and the filtrate was concentrated. The residue was purified by reverse HPLC (8 to 50% ACN-water (0.1% NH40H) with X-bridge C8 column) to give the title compound 93 mg (yield 80%) as a mixture of cis/trans isomer (ratio of 1:3). After chiral SFC separation (CL2-20×250 mm, isocratic 45% MeOH in CO2, 75% g/min flow, 220 nM UV) afforded the cis and trans enantiomes:

Workup

  1. filtrationThe reaction mixture was filtered off
  2. customto remove the catalyst
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by reverse HPLC (8 to 50% ACN-water (0.1% NH40H) with X-bridge C8 column)

Sources & evidence

ORD record
ord-bc6010e23e774e0fa86723a811d9d282
Source dataset
uspto-grants-2015_08
Patent number
US09108956B2

Reaction notes

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