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

HRID 1920937Notes

Reaction equation

HRID 1920937 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[S:24][N: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[S: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 66599256[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanolHCID 178498604HCID 178498604, compound

Product 1

HCID 674922713-[3-(5-Fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-isothiazole-5-carboxylic acid methyl esterYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-yl]-methanol (458 mg, 2.2 mmol) in THF (10 mL) was added 3-hydroxy-isothiazole-5-carboxylic acid methyl ester (350 mg, 1.9 mmol) and triphenylphosphine (692 mg, 2.6 mmol) at 0° C. under an argon atmosphere. Then diethyl azodicarboxylate (˜40% in toluene, 1.05 mL, 2.4 mmol) was added and the reaction mixture was stirred overnight at room temperature. Concentration and purification by chromatography (silica, heptane:ethyl acetate=4:1 to 0:1) afforded the title compound (488 mg, 64%) as a white solid. MS: m/e=350.1 [M+H]+.

Workup

  1. concentrationConcentration and purification by chromatography (silica, heptane:ethyl acetate=4:1 to 0:1)

Sources & evidence

ORD record
ord-750a3c6a92364ceaa2752054977f8f33
Source dataset
uspto-grants-2012_05
Patent number
US08173652B2

Reaction notes

Loading…