Acetic Acid → HCID 67171991, compound

HRID 1506556Notes

Reaction equation

HRID 1506556 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:31](=[CH:32][CH:33]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[C:20]([C:21]([F:24])([F:23])[F:22])=[C:19]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:18][N:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3]([OH:5])=[O:4].[CH3:34][Si](C=[N+]=[N-])(C)C.CC(O)=O>ClCCl.CO>[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:31](=[CH:32][CH:33]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[C:20]([C:21]([F:22])([F:23])[F:24])=[C:19]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[O:18][N:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3]([O:5][CH3:34])=[O:4]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 167693TrimethylsilyldiazomethaneHCID 67170876HCID 67170876, compound

Product 1

HCID 67171991HCID 67171991, compoundYield 97.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (Preparation 131B isomer 1, 230 mg, 0.50 mmol) in dichloromethane (5 mL) and MeOH (5 mL) was added (trimethylsilyl)diazomethane (0.42 mL, 0.84 mmol) dropwise at 0° C. The excess reagent was quenched by the slow addition of glacial AcOH (0.02 mL, 0.34 mmol) at 0° C. and the solution was concentrated. The resulting residue was mixed with ethyl acetate (30 mL). The ethyl acetate solution was washed with sat. aq. sodium bicarbonate (10 mL) and brine (10 mL), dried (sodium sulfate), filtered through a pad of silica gel, and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate:hexane 45%) to yield methyl 2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetate (230 mg, 0.489 mmol, 97% yield) as an oil: LC/MS M+1=471.09; 1H NMR (400 MHz, CDCl3) δ ppm 8.04 (1H, d, J=8.58 Hz), 7.76 (2H, d, J=7.26 Hz), 7.50-7.67 (3H, m), 7.41-7.49 (2H, m), 5.23 (1H, d, J=5.28 Hz), 3.82 (3H, s), 3.03-3.15 (4H, m).

Workup

  1. concentrationthe solution was concentrated
  2. additionThe resulting residue was mixed with ethyl acetate (30 mL)
  3. washThe ethyl acetate solution was washed with sat. aq. sodium bicarbonate (10 mL) and brine (10 mL)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered through a pad of silica gel
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate:hexane 45%)

Sources & evidence

ORD record
ord-075669b9b5c8448aae1d4f79c17d204d
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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