Triethylamine → (5-Methyl-3-pyrimidin-4-yl-isoxazol-4-yl)-methanol
Reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]=2)[C:3]=1[C:13](O)=[O:14].C(N(CC)CC)C.C(OC(Cl)=O)C.[BH4-].[Na+]>C1COCC1.O.[OH-].[Na+]>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]=2)[C:3]=1[CH2:13][OH:14]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -10 °C
Procedure
To a solution of 5-methyl-3-pyrimidin-4-yl-isoxazole-4-carboxylic acid (300 mg, 1.46 mmol) in THF (4 mL) at −10° C. was added triethylamine (203 μL, 1.46 mmol) and then a solution of ethylchloroformate (139 μL, 1.46 mmol) in THF (1 mL) added keeping the temperature below −5° C. After 1 h the mixture was filtered and the filtrate cooled to −10° C. and a suspension of sodiumborohydride (138 mg, 3.66 mmol) in water (1.5 mL) added over 15 minutes keeping the temperature below −5° C. The mixture was then allowed to warm up to room temperature over 2 h and diluted with aqueous sodium hydroxide (1 N) and extracted with ethylacetate. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, dichloromethane:methanol=9:1) afforded the title product (52.5 mg, 19%) which was obtained as white solid. MS: m/e=190.0 [M−H]−.
Workup
- customthe temperature below −5° C
- filtrationAfter 1 h the mixture was filtered
- additionadded over 15 minutes
- customthe temperature below −5° C
- temperatureto warm up to room temperature over 2 h
- extractionextracted with ethylacetate
- washThe combined organic layers were then washed with water and brine
- dry with materialdried over sodium sulfate
- customevaporated
- customPurification by chromatography (SiO2, dichloromethane:methanol=9:1)
Sources & evidence
- ORD record
- ord-52e136b5f61e4287b8fece9056733f9b
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08518974B2
Reaction notes
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