Sodium hydride → 6-Cyclopropylmethoxy-5-(3,3-difluoro-pyrrolidin-1-yl)-pyridine-2-carboxylic acid
Reaction equation
[H-].[Na+].[CH:3]1([CH2:6][OH:7])[CH2:5][CH2:4]1.C[O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:22][CH2:21][C:20]([F:24])([F:23])[CH2:19]2)=[C:14](Cl)[N:13]=1)=[O:11]>>[CH:3]1([CH2:6][O:7][C:14]2[N:13]=[C:12]([C:10]([OH:11])=[O:9])[CH:17]=[CH:16][C:15]=2[N:18]2[CH2:22][CH2:21][C:20]([F:24])([F:23])[CH2:19]2)[CH2:5][CH2:4]1Participants
Procedure
Sodium hydride (0.27 g, 8 mmol) was added in portions to cyclopropylmethanol (CAN 2516-33-8, 6 mL) and the mixture was stirred at room temperature for 2 hours. 6-Chloro-5-(3,3-difluoro-pyrrolidin-1-yl)-pyridine-2-carboxylic acid methyl ester (0.45 g, 1.6 mmol) was added to the mixture and the resulting solution was stirred in a sealed tube at 110° C. overnight. After concentration under reduced pressure, water (15 mL) was added to the residue and the solution was acidified with hydrochloric acid (6 N). The aqueous solution was extracted with ethyl acetate (3×20 mL) and the combined organic phase was washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give the target compound which was used directly in the next step without further purification; MS (EI): m/e=299.1 [M+H]+.
Workup
- stirringthe resulting solution was stirred in a sealed tube at 110° C. overnight
- concentrationAfter concentration under reduced pressure, water (15 mL)
- additionwas added to the residue
- extractionThe aqueous solution was extracted with ethyl acetate (3×20 mL)
- washthe combined organic phase was washed with brine (20 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customto give the target compound which
- customwas used directly in the next step without further purification
Sources & evidence
- ORD record
- ord-c9beedbbdd1b4e388ed8b1b13847f1dc
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290451B2
Reaction notes
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