Sodium Dithionite → N-[(4aR,6R,8aS)-8a-(5-bromo-2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 68398Notes

Reaction equation

HRID 68398 reaction equation
C([O:8][CH2:9][C@@H:10]1[O:28][CH2:27][C:13]2([C:29]3[CH:34]=[C:33]([Br:35])[C:32]([F:36])=[CH:31][C:30]=3[F:37])[N:14]=[C:15]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:16][CH2:17][CH:12]2[CH2:11]1)C1C=CC=CC=1.Br([O-])(=O)=O.[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.O>[Br:35][C:33]1[C:32]([F:36])=[CH:31][C:30]([F:37])=[C:29]([C@:13]23[CH2:27][O:28][C@@H:10]([CH2:9][OH:8])[CH2:11][C@H:12]2[CH2:17][S:16][C:15]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:14]3)[CH:34]=1

Participants

6

Reactant 3

HCID 24489Sodium DithioniteHCID 23668195Sodium BromateHCID 86762635N-[(6R)-6-[(benzyloxy)methyl]-8a-(5-bromo-2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Product 1

HCID 86762638N-[(4aR,6R,8aS)-8a-(5-bromo-2,4-difluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of C9 (3.22 g, 5.48 mmol) in ethyl acetate (100 mL) was treated with a solution of sodium bromate (4.14 g, 27.4 mmol) in water (66 mL). To the well stirred biphasic system was added a solution of sodium dithionite (4.77 g, 27.4 mmol) in water (134 mL) drop-wise over 30 minutes. The reaction mixture was stirred for 90 minutes and then diluted with ethyl acetate (500 mL). The organic layer was removed and the aqueous was extracted with ethyl acetate (3×100 mL). The combined organics were then washed with an aqueous solution of sodium thiosulfate pentahydrate (3×300 mL), brine (300 mL), and then dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) provided the product as a white solid. Yield: 1.77 g, 3.57 mmol, 65%. LCMS m/z 499.1 [M+H+], Br isotopic pattern. 1H NMR (400 MHz, CD3OD), characteristic peaks: δ 8.11 (d, J=6.5 Hz, 2H), 7.64 (t, J=7.9 Hz, 1H), 7.53-7.57 (m, 1H), 7.44-7.48 (m, 2H), 7.24 (dd, J=12, 8.3 Hz, 1H), 4.09 (dd, J=11.6, 1.9 Hz, 1H), 3.9 (d, J=11.9 Hz, 1H), 3.72-3.77 (m, 1H), 3.58 (d, J=5.1 Hz, 2H), 3.11-3.19 (m, 1H), 2.97 (dd, J=13.3, 4.1 Hz, 1H), 2.75 (dd, J=13.1, 2.7 Hz, 1H), 1.84 (q, J=11.6 Hz, 1H), 1.66-1.71 (m, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 90 minutes
  2. customThe organic layer was removed
  3. extractionthe aqueous was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organics were then washed with an aqueous solution of sodium thiosulfate pentahydrate (3×300 mL), brine (300 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8487cd88b0cf4ccfbaf2e845805f86ad
Source dataset
uspto-grants-2014_09
Patent number
US08822456B2

Reaction notes

Loading…