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

HRID 586347Notes

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-f232d5f6b7d64d7380b80dda55756ec1
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06936611B2

Reaction notes

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