Triphenylphosphine → 3-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-isoxazole-5-carboxylic acid methyl ester

HRID 1920920Notes

Reaction equation

HRID 1920920 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][OH:14])=[C:11]([CH3:15])[O:10][N:9]=2)=[N:6][CH:7]=1.[CH3:16][O:17][C:18]([C:20]1[O:24][NH:23][C:22](=O)[CH:21]=1)=[O:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:16][O:17][C:18]([C:20]1[O:24][N:23]=[C:22]([O:14][CH2:13][C:12]2[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=3)=[N:9][O:10][C:11]=2[CH3:15])[CH:21]=1)=[O:19]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2724585Methyl 3-hydroxyisoxazole-5-carboxylateHCID 66599256[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanol

Product 1

HCID 674922213-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-isoxazole-5-carboxylic acid methyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanol (438 mg, 2.1 mmol) in THF (10 mL) was added 3-oxo-2,3-dihydro-isoxazole-5-carboxylic acid methyl ester (300 mg, 2.1 mmol) and triphenylphosphine (658 mg, 2.1 mmol) at room temperature under an argon atmosphere. Then diethyl azodicarboxylate (˜40% in toluene, 1.1 mL, 2.5 mmol) was added and the reaction mixture was stirred for 3 h at room temperature. Concentration and purification by chromatography (silica, dichloromethane:methanol=4:1 to 1:4) afforded the title compound (431 mg, 62%) as a white solid. MS: m/e=334.2 [M+H]+.

Workup

  1. concentrationConcentration and purification by chromatography (silica, dichloromethane:methanol=4:1 to 1:4)

Sources & evidence

ORD record
ord-c3018a54f6e74b43a670b54b85114c59
Source dataset
uspto-grants-2012_05
Patent number
US08173652B2

Reaction notes

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