Hydrochloric Acid → 3-{4-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-hex-4-ynoic acid

HRID 1993034Notes

Reaction equation

HRID 1993034 reaction equation
[OH-].[K+].C([O:5][C:6](=[O:36])[CH2:7][CH:8]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:14][CH:13]=1)[C:9]#[C:10][CH3:11])C.Cl>C(O)C.O>[CH3:25][C:24]1[O:23][C:22]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:34])([F:33])[F:35])=[CH:28][CH:27]=2)=[N:21][C:20]=1[CH2:19][O:18][C:15]1[CH:14]=[CH:13][C:12]([CH:8]([C:9]#[C:10][CH3:11])[CH2:7][C:6]([OH:36])=[O:5])=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 591326383-{4-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

Product 1

HCID 591327373-{4-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-hex-4-ynoic acidYield 52%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

2N KOH(aq) was added to a solution of 18.3 (304 mg, 0.65 mmol) in ethanol (5 mL). The reaction was stirred at room temperature overnight and then taken up in copious water. The aqueous solution was adjusted to pH=2.0 with 1N HCl(aq) and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, followed by brine. The solvent was removed under reduced pressure and the resulting residue was purified via radial chromatography (40% ethyl acetate in Hexanes+0.1% AcOH) to yield 150 mg (52%) of compound 18 as a glass. LC/MSD m/e: 444.0 (M+H); 1H NMR (400 MHz) (acetone) ∂ 8.21 (2H, m), 7.89 (2H, d, J=8.0 Hz), 7.38 (2H, m), 7.03 (2H, m), 5.06 (2H, s), 4.06 (1H, m), 2.70 (2H, m), 2.52 (3H, s), 1.81 (3H, s).

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washThe combined organic layers were washed with water
  3. customThe solvent was removed under reduced pressure
  4. customthe resulting residue was purified via radial chromatography (40% ethyl acetate in Hexanes+0.1% AcOH)

Sources & evidence

ORD record
ord-17771d5bf91c45f98853e81ec66a1f09
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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