Diisopropylethylamine → tert-Butyl 4-(thiazol-4-ylmethyl)piperazine-1-carboxylate

HRID 416905Notes

Reaction equation

Cl[CH2:2][C:3]1[N:4]=[CH:5][S:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:17]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>C(Cl)Cl.CCOC(C)=O>[S:6]1[CH:7]=[C:3]([CH2:2][N:27]2[CH2:26][CH2:25][N:24]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:29][CH2:28]2)[N:4]=[CH:5]1

Participants

Conditions

Temperature: 35 °C

Procedure

4-(Chloromethyl)thiazole (0.500 g, 2.94 mmol, 1 eq) was suspended in DCM (4.6 mL). DIPEA (1.28 mL, 7.35 mmol, 2.5 eq) was added dropwise, followed by N-Boc-piperazine (1.200 g, 6.47 mmol, 2.2. eq). The mixture was stirred at 35° C. for 5 h, diluted with EtOAc and washed with H2O and brine. The organic layer was separated, dried (MgSO4) and the solvent was removed in vacuo. The crude product was purified by column chromatography on a Biotage SP1 system (DCM/EtOAc; v/v 1:1) to give the title compound as a clear oil (0.160 g, 19%); 1H-NMR (500 MHz, CDCl3): δ 1.46 (s, 9H, C(CH3)3), 2.47 (br t, J=4.2 Hz, 4H, piperazine N(CH2)2), 3.46 (br t, J=4.5 Hz, 4H, piperazine N(CH2)2), 3.75 (s, 2H, NCH2), 7.20 (s, 1H, thiazole 5-H), 8.79 (s, 1H, thiazole 2-H); LC (Method B)-MS (ESI, m/z): Rt=1.80 min—284 [(M+H)+, 100%].

Workup

washwashed with H2O and brine
customThe organic layer was separated
dry with materialdried (MgSO4)
customthe solvent was removed in vacuo
customThe crude product was purified by column chromatography on a Biotage SP1 system (DCM/EtOAc; v/v 1:1)

Sources & evidence

ORD record: ord-a43c6cd91e3b40af839382c3dd29e636
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Reaction notes

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