Lithium Hydroxide → 4-(2-Carboxy-4-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1810993Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

4-(4-Fluoro-2-methoxycarbonyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (5.5 g, 16.2 mmol) is dissolved in THF (40 mL) and 1 M aqueous LiOH (33 mL) is added at room temperature. The solution is warmed to 50° C. for 3 h. THF is removed under reduced pressure and the aqueous part is washed with 50% EtOAc in hexane. The aqueous part is acidified with 1 M aqueous HCl followed by extraction with EtOAc (3×50 mL). Combined organic layer is dried over anhydrous MgSO4 and concentrated under reduced pressure to afford 4-(2-carboxy-4-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a solid (4.9 g, 98%).

Workup

customTHF is removed under reduced pressure
washthe aqueous part is washed with 50% EtOAc in hexane
extractionfollowed by extraction with EtOAc (3×50 mL)
dry with materialCombined organic layer is dried over anhydrous MgSO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-4ea2407a09034e6aad209ad6ed4612d5
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362249B2

Reaction notes

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