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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 515392
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HRID 515392 반응식
[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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 9942167Palladium hydroxide용매

실험 절차

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:

후처리

  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)

출처 및 근거

ORD 기록
ord-bc6010e23e774e0fa86723a811d9d282
출처 데이터셋
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09108956B2

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