Acetone → Methyl 4-{1,2-dihydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}benzoate

HRID 1040184

Reaction equation

HRID 1040184 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]([C:26]3[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=3)=[CH2:25])=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[OH2:36].Cl.CC(C)=[O:40]>[O-]S([O-])=O.[Na+].[Na+].CCOC(C)=O.[Os](=O)(=O)(=O)=O>[OH:36][C:24]([C:26]1[CH:27]=[CH:28][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:34][CH:35]=1)([C:22]1[S:23][C:19]([C:4]2[CH:5]=[C:6]([NH:8][C:9]3[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=3)[CH:7]=[C:2]([CH3:1])[CH:3]=2)=[CH:20][N:21]=1)[CH2:25][OH:40]

Participants

8

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 962WaterHCID 67257947Methyl 4-{1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethenyl}benzoate

Product 1

HCID 67433739Methyl 4-{1,2-dihydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}benzoateYield 65.5%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 8857Ethyl AcetateSolventHCID 24437Sodium SulfiteSolvent

Procedure

To a solution of the product from Step 1 (0.100 g, 0.201 mmol) and 4-methylmorpholine n-oxide (0.047 g, 0.403 mmol) in acetone (2.98 ml)/water (0.373 ml) was added osmium tetroxide (4% by weight in water, 0.158 ml, 0.020 mmol), and the mixture was stirred at room temperature. Upon completion by LCMS, the mixture was diluted with aqueous 10% Na2SO3 and EtOAc. The aqueous layer was acidified (pH 3-4) with 1 N HCl and extracted with 10% IPA/CHCl3. The combined organic layers were dried (Na2SO4), filtered and concentrated. A combination of chromatography on silica gel (Biotage 250 SNAP, 0-10% MeOH/DCM) and reverse phase HPLC (10-90% ACN/1-120) afforded methyl 4-{1,2-dihydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}benzoate (70 mg, 0.132 mmol, 65.5% yield). MS ESI: [M+H]+ m/z 531.1.

Workup

  1. extractionextracted with 10% IPA/CHCl3
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-279471e49d9447c29e17094ac7116102
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Linked notes

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