Bromoacetic Acid → [1-(4-Methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-acetic acid tert-butyl ester

HRID 720448Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=[O:18])[NH:15][CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:22])([F:21])[F:20])=[N:10]2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:26][C:27]([OH:29])=[O:28]>CN(C=O)C>[C:12]([O:29][C:27](=[O:28])[CH2:26][N:15]1[CH2:16][CH2:17][C:12]2[C:11]([C:19]([F:22])([F:20])[F:21])=[N:10][N:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[C:13]=2[C:14]1=[O:18])([CH3:17])([CH3:13])[CH3:11]

Participants

Conditions

Temperature: 0 °C

Procedure

Part A: 1-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (2.0 g, 6.43 mmol) was stirred in dry DMF (8 mL) at 0° C. NaH (60%, 0.35 g, 8.75 mmol, 1.4 eq) was added. Bromoacetic acid and t-butyl ester (1.0 mL, 6.77 mmol, 1.1 eq) were added dropwise. The mixture was stirred at 0° C. for 2 h and at rt overnight. The reaction was quenched with H2O, extracted with EtOAc, washed with brine, concentrated, and purified by silica gel chromatography (1:1 EtOAc:hexanes) to give pure [1-(4-methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-acetic acid tert-butyl ester (2.73 g, yield: 99%).

Workup

customThe reaction was quenched with H2O
extractionextracted with EtOAc
washwashed with brine
concentrationconcentrated
custompurified by silica gel chromatography (1:1 EtOAc:hexanes)

Sources & evidence

ORD record: ord-d6be77d212fc42f7a165350b3ced3ea9
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07135469B2

Reaction notes

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