tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(5-bromo-1,3-thiazol-2-yl)piperazine-1-carboxylate

HRID 1926341Notes

Reaction equation

Br[C:2]1[S:3][C:4]([Br:7])=[CH:5][N:6]=1.[N:8]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1>CCN(C(C)C)C(C)C>[C:17]([O:16][C:14]([N:8]1[CH2:13][CH2:12][N:11]([C:2]2[S:3][C:4]([Br:7])=[CH:5][N:6]=2)[CH2:10][CH2:9]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of 2,5-dibromothiazole (1.00 g, 4.12 mmol) in DIPEA (3.00 mL) was charged with tert-butyl 1-piperazinecarboxylate (0.767 g, 4.12 mmol) and heated to 110° C. for 3 h and then an additional 16 h at rt. The reaction mixture was partitioned between CHCl3 and H2O, and the layers were separated. The aqueous layer was re-extracted with CHCl3 (3×) and the combined organic fractions were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel [eluting with 0.5% EtOAc in CHCl3] resulting in the title compound as a light orange solid. 1H NMR (400 MHz, CDCl3): δ=1.47 (s, 9H), 3.37-3.44 (m, 4H), 3.51-3.59 (m, 4H), 7.08 (s, 1H). MS (ES+): m/z=348.09 (51/49) [MH+]. HPLC: tR=3.73 min (ZQ2, polar—5 min).

Workup

customan additional 16 h
customat rt
customThe reaction mixture was partitioned between CHCl3 and H2O
customthe layers were separated
extractionThe aqueous layer was re-extracted with CHCl3 (3×)
dry with materialthe combined organic fractions were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by chromatography on silica gel [eluting with 0.5% EtOAc in CHCl3]

Sources & evidence

ORD record: ord-4e76e07e917949809c12549226636327
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178668B2

Reaction notes

Loading…