dimethylsulfoxide THF → (+)-1-(4-{2-[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-cyclopropanecarboxylic acid

HRID 1678645Notes

Reaction equation

HRID 1678645 reaction equation
C([O:5][C:6]([C:8]1([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:43])[CH:20]([C:27]3[N:28]([C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=4)[N:29]=[C:30]4[C:35]=3[CH2:34][CH2:33][CH2:32][CH2:31]4)[CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[C:14]([F:44])[CH:13]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C1COCC1.CS(C)=O>C(O)(C)C.C(O)=O>[Cl:42][C:39]1[CH:38]=[CH:37][C:36]([N:28]2[C:27]([CH:20]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:19]([NH:18][C:15]3[CH:16]=[CH:17][C:12]([O:11][C:8]4([C:6]([OH:7])=[O:5])[CH2:10][CH2:9]4)=[CH:13][C:14]=3[F:44])=[O:43])=[C:35]3[C:30]([CH2:31][CH2:32][CH2:33][CH2:34]3)=[N:29]2)=[CH:41][CH:40]=1

Participants

5

Reactant 2

HCID 21830753dimethylsulfoxide THFHCID 67130978(+)-1-(4-{2-[2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-cyclopropanecarboxylic acid tert-butyl ester

Product 1

HCID 45110644(+)-1-(4-{2-[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-cyclopropanecarboxylic acidYield 100%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 3776IsopropanolSolvent

Procedure

A solution of (+)-1-(4-{2-[2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-cyclopropanecarboxylic acid tert-butyl ester (22 mg, 35 umol; example 21.5) in isopropanol (200 ul) and formic acid (400 ul) was stirred at 90° C. for 2 h. The mixture was poured onto ice water/brine 1/1 and extracted two times with iPrOAc. The combined extracts were washed with ice water/brine 1/1 and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give the title compound (20 mg, 35 umol; quant; 100% ee) as yellow foam. MS: m/e=566.3 [M+H+].

Workup

  1. extractionextracted two times with iPrOAc
  2. washThe combined extracts were washed with ice water/brine 1/1
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration the solvent
  5. customwas removed under reduced pressure

Sources & evidence

ORD record
ord-8852ad3059344f719c7c6143278516da
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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