Triphenylphosphine → 1-methyl-5-(5-methyl-3-pyridin-2-yl-isoxazol-4-ylmethoxy)-1H-pyrazole-3-carboxylic acid methyl ester

HRID 1695462

Reaction equation

HRID 1695462 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([OH:10])[N:7]([CH3:11])[N:6]=1)=[O:4].[CH3:12][C:13]1[O:17][N:16]=[C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[C:14]=1[CH2:24]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([O:10][CH2:24][C:14]2[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)=[N:16][O:17][C:13]=2[CH3:12])[N:7]([CH3:11])[N:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 66643722HCID 66643722, compoundHCID 178498595HCID 178498595, compound

Product 1

HCID 666463331-methyl-5-(5-methyl-3-pyridin-2-yl-isoxazol-4-ylmethoxy)-1H-pyrazole-3-carboxylic acid methyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-hydroxy-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester (400 mg, 2.6 mmol) and (5-methyl-3-pyridin-2-yl-isoxazol-4-yl)-methanol (500 mg, 2.6 mmol) in THF (10 mL) at 5° C. under argon was added triphenylphosphine (862 mg, 3.3 mmol), then diethyl azodicarboxylate (573 mg, 3.3 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was then evaporated. Purification by chromatography (silica, dichloromethane:methanol=9:1) then purification using a 5×50 cm Chiralpak AD column at room temperature using an isopropanol:heptane (2:8) mobile phase with UV detection at 220 nM afforded the title compound (400 mg, 48%) as a white solid. MS: m/e=328.3 [M+H]+.

Workup

  1. customThe reaction mixture was then evaporated
  2. customPurification by chromatography (silica, dichloromethane:methanol=9:1)
  3. custompurification
  4. customat room temperature

Sources & evidence

ORD record
ord-6768a91f037f41bf9c3eff9e6bfae10b
Source dataset
uspto-grants-2012_04
Patent number
US08163728B2

Linked notes

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