Diisopropylethylamine → tert-Butyl 4-((2-methylthiazol-4-yl)methyl)piperazine-1-carboxylate

HRID 416884Notes

Reaction equation

Cl[CH2:2][C:3]1[N:4]=[C:5]([CH3:8])[S:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:18]([N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C(Cl)Cl.CCOC(C)=O>[CH3:8][C:5]1[S:6][CH:7]=[C:3]([CH2:2][N:28]2[CH2:27][CH2:26][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:30][CH2:29]2)[N:4]=1

Participants

Conditions

Temperature: 35 °C

Procedure

4-(Chloromethyl)-2-methyl-thiazole (0.590 g, 3.18 mmol, 1 eq) was suspended in DCM (5 mL). DIPEA (1.39 mL, 7.95 mmol, 2.5 eq) was added dropwise, followed by N-Boc-piperazine (1.300 g, 7.0 mmol, 2.2. eq). The mixture was stirred at 35° C. for 5 h, then diluted with EtOAc, and washed with H2O and brine. The organic layer was separated, dried (MgSO4) and the solvent 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 (0.940 g, 99%); 1H-NMR (500 MHz, CDCl3): δ 1.47 (s, 9H, C(CH3)3), 2.47 (t, 4H, J=4.5 Hz, piperazine N(CH2)2), 2.73 (s, 3H, Me), 3.48 (t, 4H, J=4.5 Hz, piperazine N(CH2)2), 3.64 (s, 2H, NCH2), 6.96 (s, 1H, thiazole 5-H); LC (Method B)-MS (ESI, m/z): Rt=1.96 min—298 [(M+H)+, 100%].

Workup

washwashed with H2O and brine
customThe organic layer was separated
dry with materialdried (MgSO4)
customthe solvent 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-b189d1774e41449d8505b3674cb029ed
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Reaction notes

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