Ethyl Acetate → tert-Butyl 4-(2-oxo-2-(thiazol-2-yl)ethyl)piperazine-1-carboxylate

HRID 496609Notes

Reaction equation

C([Li])CCC.Br[C:7]1[S:8][CH:9]=[CH:10][N:11]=1.CON(C)[C:15](=[O:30])[CH2:16][N:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.C(OCC)(=O)C>C(OCC)C.O1CCCC1.O>[C:23]([N:20]1[CH2:19][CH2:18][N:17]([CH2:16][C:15](=[O:30])[C:7]2[S:8][CH:9]=[CH:10][N:11]=2)[CH2:22][CH2:21]1)([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]

Participants

Conditions

Temperature: -78 °C

Procedure

n-Butyl lithium (1 M in hexanes, 12.2 mL, 12.2 mmol) was slowly added to a solution of 2-bromothiazole (2.0 g, 12.2 mmol) in diethyl ether (50 mL) at −78° C. The mixture stirred at −78° C. for 1 h. Then, a solution of N-methoxy-N-methyl-4-Boc-piperazin-1-ylacetamide (3.0 g, 10.4 mmol) in tetrahydrofuran was slowly added. The mixture was allowed to slowly warm to −20° C. and stirred for 4 h. The mixture was then diluted with water followed by ethyl acetate. The water layer was extracted with ethyl acetate and the organic layers were combined, washed with brine, dried (Na2SO4), filtered, and concentrated. The crude product was purified by chromatography (Sio2, 20:1-6:1 CH2Cl2:CMA) to provide 1-Boc-4-(2-oxo-2-thiazol-2-ylethyl)piperazine (2.2 g, 68%) as a colorless oil.

Workup

temperatureto slowly warm to −20° C.
stirringstirred for 4 h
extractionThe water layer was extracted with ethyl acetate
washwashed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by chromatography (Sio2, 20:1-6:1 CH2Cl2:CMA)

Sources & evidence

ORD record: ord-36be8108a7354d95bd0c71eca536c404
Source dataset: uspto-grants-2005_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06946467B2

Reaction notes

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