Lithium Hydroxide → [4-(4-Methoxy-3-methyl-benzoyl)-piperidin-1-yl]-acetic acid

HRID 713446Notes

Reaction equation

C([O:3][C:4](=[O:23])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12](=[O:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([CH3:21])[CH:14]=2)[CH2:8][CH2:7]1)C.[Li+].[OH-].[Li+].[Cl-]>C1COCC1.CO>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]([CH:9]2[CH2:10][CH2:11][N:6]([CH2:5][C:4]([OH:23])=[O:3])[CH2:7][CH2:8]2)=[O:22])=[CH:14][C:15]=1[CH3:21]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of [4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-acetic acid ethyl ester (0.19 g, 0.60 mmol) in 6 mL of THF and 2 mL of MeOH, was added LiOH (0.13 g, 3.0 mmol in 3 mL of water). After 1.5 hours at ambient temperature the solvent was removed in vacuo, then diluted with 20 mL of water (pH 14). The residue was treated with 12 mL of 1N HCl (pH 4), frozen at −78° C. then lyophilized for 24 hours to yield the title product (0.17 g, 0.54 mmol, 90%) with LiCl salt. MS (ESI) m/z 291.8 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 1.58 min.

Workup

customAfter 1.5 hours at ambient temperature the solvent was removed in vacuo
additiondiluted with 20 mL of water (pH 14)
additionThe residue was treated with 12 mL of 1N HCl (pH 4)

Sources & evidence

ORD record: ord-f2238d890d25468798379579b8b9d1a7
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181266B2

Reaction notes

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