Ammonia → {6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-3-methyl-1,2-benzothiazol-5-yl}methanol

HRID 577902Notes

Reaction equation

HRID 577902 reaction equation
C([SiH2][O:6][C:7](C1C=CC=CC=1)(C1C=CC=CC=1)[C:8]1[C:9]([N:19]2[CH2:24][C@H:23]([CH3:25])[O:22][C@H:21]([CH3:26])[CH2:20]2)=[C:10]([F:18])C(F)=[C:12]([C:14](=O)[CH3:15])[CH:13]=1)(C)(C)C.[S].[I-].[K+].[NH3:42].C[S:44]([CH3:46])=O>O>[CH3:26][C@H:21]1[O:22][C@@H:23]([CH3:25])[CH2:24][N:19]([C:9]2[C:8]([CH2:7][OH:6])=[CH:13][C:12]3[C:14]([CH3:15])=[N:42][S:44][C:46]=3[C:10]=2[F:18])[CH2:20]1

Participants

7

Reactant 5

HCID 222AmmoniaHCID 679Dimethyl SulfoxideHCID 4875Potassium IodideHCID 5362487SulfurHCID 178466840HCID 178466840, compound2×

Product 1

HCID 67357470{6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-3-methyl-1,2-benzothiazol-5-yl}methanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-[5-(tert-Butyldiphenylsilanyloxymethyl)-4-[(2R,6S)-2,6-dimethyl-morpholin-4-yl]-2,3-difluorophenyl]ethanone (Intermediate 9, 0.5 g, 0.92 mmol), sulfur powder (0.06 g, 1.8 mmol), potassium iodide (0.08 g, 0.4 mmol) and 25% aqueous ammonia solution (10 mL) in DMSO (10 mL) was heated in a sealed tube at 100° C. for 4 hours. The reaction mixture was cooled and water was added. The mixture was extracted with ethyl acetate, which was dried (Na2SO4) and concentrated. The residue was purified by column chromatography (1:9 ethyl acetate:hexanes) to afford product as a yellow solid. Yield: 0.18 g (63%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionThe mixture was extracted with ethyl acetate, which
  3. dry with materialwas dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (1:9 ethyl acetate:hexanes)
  6. customto afford product as a yellow solid

Sources & evidence

ORD record
ord-50dd621248194ae0a662c013442697b7
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

Loading…