Trimethylsilyldiazomethane → Methyl 5-isobutylisoxazole-3-carboxylate

HRID 1506320Notes

Reaction equation

HRID 1506320 reaction equation
[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=[O:11])[CH:6]=1)[CH:2]([CH3:4])[CH3:3].[CH3:13][Si](C=[N+]=[N-])(C)C>ClCCl.CO>[CH2:1]([C:5]1[O:9][N:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:6]=1)[CH:2]([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 11336425-(2-Methylpropyl)-1,2-oxazole-3-carboxylic acid

Product 1

HCID 3477558Methyl 5-isobutylisoxazole-3-carboxylateYield 85.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-isobutylisoxazole-3-carboxylic acid (1.0 g, 5.91 mmol) in a mixture of dichloromethane (18 mL) and methanol (6 mL) was added trimethylsilyldiazomethane (2.0 M in ether) (5.91 mL, 11.8 mmol) dropwise until the yellow color persisted and the bubbling ceased (˜3.9 mL was required). The solvent was removed under reduced pressure, and the residue was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by flash silica gel chromatography using a 5% mixture of ethyl acetate in hexane afforded methyl 5-isobutylisoxazole-3-carboxylate (0.925 g, 5.05 mmol, 85% yield) as a flakey, white solid. The product had an HPLC ret. time=1.83 min.−Column: (condition A); LC/MS M+1=184.1. 1H NMR (500 MHz, CDCl3) δ ppm [mixture of isobutyl rotomers] 0.96-1.00 (m, 6H), [1.94-2.03 (m, 0.1H) and 2.03-2.14 (m, 0.9H)], [2.62 (d, J=7.21 Hz, 0.2H) and 2.70 (d, J=7.21 Hz, 1.8H)], 3.96-3.99 (m, 3H), and [6.41-6.44 (m, 0.9H) and 6.80 (s, 0.1H)].

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with dichloromethane
  3. washwashed with a saturated aqueous solution of sodium bicarbonate
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration under reduced pressure
  6. customfollowed by purification by flash silica gel chromatography

Sources & evidence

ORD record
ord-1ccf8f1ec4584d1bb7cb51934bd774ea
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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