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

HRID 1454200노트

반응식

HRID 1454200 반응식
[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

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 575293223-Bromo-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester

생성물 1

HCID 575293353-Acetyl-5-(1,1-dioxo-1lambda6-[1,2]thiazinan-2-yl)-benzoic acid methyl ester수율 44.6%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
122 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-ab7ede4c4f10486babbe1709374c16ed
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07476764B2

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