Potassium Carbonate → tert-Butyl 4-(7-fluoro-6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)piperidine-1-carboxylate

HRID 424596Notes

Reaction equation

[F:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([NH:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[C:4]([S:25][CH2:26][CH2:27]I)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]2[N:11]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[CH2:27][CH2:26][S:25][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of tert-butyl 4-(4-fluoro-2-(2-iodoethylthio)-5-nitrophenylamino)piperidine-1-carboxylate (394 mg, 0.750 mmol) in DMF (5 mL) was added potassium carbonate (207 mg, 1.500 mmol), and the resulting mixture was stirred at 60° C. for 2 hours and then at 90° C. overnight. The mixture was then cooled to room temperature, diluted with ethyl acetate, and washed with saturated sodium carbonate (3×), water, and brine. The organic phase was dried, filtered, concentrated, and then chromatographed using 1:9 ethyl acetate:hexanes giving the desired product (193 mg, 64.7%) as a red foam. 1H NMR (DMSO-d6) δ 7.42 (d, J=6.6 Hz, 1H), 7.30 (d, J=11.7 Hz, 1H), 4.10-3.95 (m, 2H), 3.91-3.79 (m, 1H), 3.41-3.36 (m, 2H), 3.13-3.09 (m, 2H), 2.99-2.78 (m, 2H), 1.73-1.63 (m, 2H), 1.63-1.51 (m, 2H), 1.41 (s, 9H); ESI-MS (m/z, %): 420 (MNa+, 52), 398 (MH+, 35), 342 (100), 298 (64).

Workup

customat 90° C.
customovernight
temperatureThe mixture was then cooled to room temperature
washwashed with saturated sodium carbonate (3×), water, and brine
customThe organic phase was dried
filtrationfiltered
concentrationconcentrated
customchromatographed

Sources & evidence

ORD record: ord-88d2d5edb9924d16883eb2cac1e1ebda
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106043B2

Reaction notes

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