Hydrochloric Acid → (5R)-5-(3,5-difluorophenyl)-2,2-dimethylthiomorpholin-3-one

温度

115 °C

To a solution of methyl 2-{[(2R)-2-[(tert-butylsulfinyl)amino]-2-(3,5-difluorophenyl)ethyl]thio}-2-methylpropanoate from Step C (428 mg, 1.09 mmol) in MeOH (20 mL), cooled to 0° C., was added anhydrous HCl gas for 1 minute. The reaction was sealed and allowed to sit at 0° C. for fifteen minutes, after which nitrogen was bubbled through the reaction for twenty minutes. The reaction was concentrated in vacuo. Additional MeOH (30 mL) was added and it was again concentrated in vacuo. This was repeated with another addition of MeOH and triethylamine (440. mg, 4.35 mmol). To the resulting residue was added toluene (10 mL) and triethylamine (440. mg, 4.35 mmol). A reflux condenser was attached and the mixture stirred at 115° C. After one week of stirring, the reaction was judged to be 90% complete by LCMS. The mixture was cooled to ambient temperature and concentrated in vacuo. The residue was diluted with diethyl ether (50 mL) and washed individually with 20 mL of each of the following aqueous solutions: 1 M HCl (twice), water, and saturated brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue that was purified by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2—1:99 to 5:95, to give the title compound. MS: m/z=258 (M+1).

1. customThe reaction was sealed
2. waitto sit at 0° C. for fifteen minutes
3. customafter which nitrogen was bubbled through the reaction for twenty minutes
4. concentrationThe reaction was concentrated in vacuo
5. additionAdditional MeOH (30 mL) was added
6. concentrationit was again concentrated in vacuo
7. customA reflux condenser was attached
8. stirringAfter one week of stirring
9. temperatureThe mixture was cooled to ambient temperature
10. concentrationconcentrated in vacuo
11. additionThe residue was diluted with diethyl ether (50 mL)
12. washwashed individually with 20 mL of each of the following aqueous solutions
13. dry with materialThe organic layer was then dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customto give a residue that
17. customwas purified by silica gel chromatography
18. washeluting with a gradient of MeOH

ORDレコード

ord-1690bc0165804dd0a230574f365e55a8

出典データセット

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07893079B2