Hydrochloric Acid → 3-Acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester

HRID 1454200Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][S:11]2(=[O:17])=[O:16])[CH:7]=[C:6](Br)[CH:5]=1.[CH:20]([O:22]CCCC)=[CH2:21].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][S:11]2(=[O:17])=[O:16])[CH:7]=[C:6]([C:20](=[O:22])[CH3:21])[CH:5]=1

Participants

Conditions

Temperature: 122 °C

Procedure

A mixture of 3-bromo-5-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester (500 mg, 1.44 mmol), 1-(vinyloxy)butane (288.6 mg, 0.37 mL, 2.88 mmol), palladium acetate (9.6 mg, 0.043 mmol), DPPP (39.2 mg, 0.095 mmol) and potassium carbonate (238.5 mg, 1.73 mmol) in DMF (3.8 mL) and H2O (0.45 mL) in a Smith process vial was heated at 122° C. in microwave for 3 h. The reaction mixture was cooled down to room temperature and hydrolyzed by addition of 5% HCl (6 mL) slowly. The reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum. The crude mixture was purified by reverse phase prep HPLC to give the title compound (200 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 1.93-2.01 (2H, m), 2.31-2.37 (2H, m), 2.67 (3H, s), 3.27-3.30 (2H, m), 3.83 (2H, t, J=5 Hz), 3.98 (3H, s), 8.14 (1H, m), 8.19 (1H, m), 8.51 (1H, m). HPLC retention time: 1.448 min (method A). MS (ESI) (M+H)+ 312.13.

Workup

extractionThe reaction mixture was worked up by extraction with ethyl acetate and concentration under vacuum
customThe crude mixture was purified by reverse phase prep HPLC

Sources & evidence

ORD record: ord-ab7ede4c4f10486babbe1709374c16ed
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07476764B2

Reaction notes

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