Cyclopentanol → Cyclopentyl 3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolecarboxylate

HRID 2423483Notes

Reaction equation

HRID 2423483 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:10][C:11]1[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:14]([CH:20]([CH3:22])[CH3:21])[O:13][N:12]=1>C1COCC1>[CH:1]1([O:6][CH2:10][C:11]2[C:15]([C:16]([O:18][CH:19]3[CH2:3][CH2:2][CH2:1][CH2:5]3)=[O:17])=[C:14]([CH:20]([CH3:22])[CH3:21])[O:13][N:12]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7298CyclopentanolHCID 24758Sodium hydrideHCID 59321482Methyl 3-(bromomethyl)-5-(1-methylethyl)-4-isoxazolecarboxylate

Product 1

HCID 59321532Cyclopentyl 3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolecarboxylateYield 15.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of cyclopentanol (0.44 mL, 4.8 mmol), in THF (10 mL), was stirred at 0° C. as sodium hydride 60% oil dispersion (192 mg, 4.8 mmol) was added. The solution was allowed to stir for 30 minutes. A solution of methyl 3-(bromomethyl)-5-(1-methylethyl)-4-isoxazolecarboxylate (500 mg, 1.91 mmol), in THF (5 mL) was then added and the resulting solution was allowed to warm to room temperature and stir for 3 hours. The solution was then partitioned between brine and ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The residue purified by chromatography (silica gel, hexane to 1:4 ethyl acetate:hexanes). Fractions containing the product were combined and concentrated to yield cyclopentyl 3-[(cyclopentyloxy)methyl]-5-(1-methylethyl)-4-isoxazolecarboxylate (94 mg, 15%). 1H NMR (400 MHz, DMSO-d6): δ 5.29-5.26 (m, 1H), 4.54 (s, 2H), 3.98 (m, 1H), 3.64 (septet, 7 Hz, 1H), 1.85 (m, 2H), 1.72-1.56 (m, 12H), 1.47-1.40 (m, 2H), 1.25 (d, J=7 Hz, 6H). ESI-LCMS m/z 322 (M+H)+.

Workup

  1. additionwas added
  2. stirringstir for 3 hours
  3. customThe solution was then partitioned between brine and ethyl acetate
  4. dry with materialThe organic layer was dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue purified by chromatography (silica gel, hexane to 1:4 ethyl acetate:hexanes)
  8. additionFractions containing the product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ae58cbc90dc94d57bee35c6e7cf296ac
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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