Water → 2-[1-[(2,5-Dimethylphenyl)acetyl]-4-piperidinyl]-4-oxazolecarboxylic acid

HRID 2043734Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[O:19][CH:20]=[C:21]([C:23]([O:25]C)=[O:24])[N:22]=2)[CH2:14][CH2:13]1)=[O:11].O.[OH-].[Na+]>O1CCCC1.[Cl-].[Na+]>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[O:19][CH:20]=[C:21]([C:23]([OH:25])=[O:24])[N:22]=2)[CH2:14][CH2:13]1)=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

Methyl 2-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-4-oxazolecarboxylate (i.e. the product of Example 9, Step E) (665 mg, 1.87 mmol) was dissolved in 5 mL tetrahydrofuran, and 3.3 mL of water was added. The reaction mixture was cooled to 0° C. with vigorous stirring. A 1 N aqueous sodium hydroxide solution (3.7 mL) was added dropwise, and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with saturated sodium chloride solution (4 mL), washed with diethyl ether, and the aqueous phase was acidified to pH 3-4 by dropwise addition of 20% citric acid solution. The precipitated solid was filtered and dried to give 490 mg of the title compound. 1H NMR (DMSO-d6) δ 1.55 (m, 2H), 2.0 m, 2H), 2.14 (s, 3H), 2.23 (s, 3H), 2.85 (m, 1H), 3.1-3.3 (m, 2H), 3.65 (m, 2H), 3.9 (m, 1H), 4.35 (m, 1H), 6.8-7.1 (m, 3H), 8.66 (s, 1H), 13.0 (s, 1H).

Workup

washwashed with diethyl ether
additionthe aqueous phase was acidified to pH 3-4 by dropwise addition of 20% citric acid solution
filtrationThe precipitated solid was filtered
customdried

Sources & evidence

ORD record: ord-a914cf62f82f447388f2351ac6a74b63
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586611B2

Reaction notes

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