Lithium Hydroxide → (4-Bromo-2,6-dimethyl-phenyl)-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone

HRID 1692377Notes

Reaction equation

[Br:1][C:2]1[CH:30]=[C:29]([CH3:31])[C:5]([C:6]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@H:15]3[CH2:19][O:20]C(=O)C3C=CC=CC=3)[CH2:10][CH2:9]2)=[O:7])=[C:4]([CH3:32])[CH:3]=1.[OH-].[Li+]>C1COCC1.CO>[Br:1][C:2]1[CH:3]=[C:4]([CH3:32])[C:5]([C:6]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@H:15]3[CH2:19][OH:20])[CH2:12][CH2:13]2)=[O:7])=[C:29]([CH3:31])[CH:30]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2.20 g (4.4 mmol) of benzoic acid (S)-1-[1-(4-bromo-2,6-dimethyl-benzoyl)-piperidin-4-yl]-pyrrolidin-2-ylmethyl ester in 120 ml of THF/MeOH (1:1) was added 11.0 ml (11.0 mmol) of lithium hydroxide solution (1 molar in water) drop by drop and the reaction mixture was then heated up to 50° C. After 2 hours, the solvents were evaporated and the residue poured into crashed ice and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 1.19 g (68%) of the title compound as light yellow oil. MS: 395.2 (MH+, 1 Br).

Workup

customthe solvents were evaporated
additionthe residue poured
extractionextracted twice with CH2Cl2
washthe organic phases were washed with water
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated
customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record: ord-1eb305dbd0de493c9d25c931b8d97989
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153805B2

Reaction notes

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