Sodium Thiosulfate → (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-N-(1-oxopropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxamide

HRID 68420Notes

Reaction equation

HRID 68420 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[C:23]([NH:31][C:32]1[S:33][CH2:34][C@@H:35]2[CH2:41][C@H:40]([C:42]([NH:44][CH:45]([CH3:48])[CH2:46][OH:47])=[O:43])[O:39][CH2:38][C@:36]2([C:49]2[CH:54]=[C:53]([Br:55])[CH:52]=[CH:51][C:50]=2[F:56])[N:37]=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl.C(OCC)C>[C:23]([NH:31][C:32]1[S:33][CH2:34][C@@H:35]2[CH2:41][C@H:40]([C:42]([NH:44][CH:45]([CH3:48])[CH:46]=[O:47])=[O:43])[O:39][CH2:38][C@:36]2([C:49]2[CH:54]=[C:53]([Br:55])[CH:52]=[CH:51][C:50]=2[F:56])[N:37]=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 86762657(4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-N-(1-hydroxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxamide

Product 1

HCID 86762658(4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-N-(1-oxopropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Dess-Martin periodinane (1.04 g, 2.44 mmol) was added to a solution of (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-N-(1-hydroxypropan-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxamide (C38) (0.897 g, 1.63 mmol) in dichloromethane (75 mL). The resulting solution was left stirring overnight at room temperature. The reaction mixture was diluted with diethyl ether (100 mL), a saturated aqueous solution of sodium bicarbonate (50 mL) and a 10% aqueous solution of sodium thiosulfate (50 mL). The layers were separated and the resulting aqueous layer was further extracted with diethyl ether (2×100 mL). The combined organics were then washed with water (100 mL), brine (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the product as a white solid. Yield 747 mg, 84%. LCMS m/z 532.1 [M+H+]. 1H NMR (400 MHz, CD3OD) characteristic peaks: δ 9.47 (d, J=6.7 Hz, 1H), 8.11 (br d, J=6.7 Hz, 2H), 7.46-7.60 (m, 4H), 7.18 (dd, J=12.1, 9.2 Hz, 1H), 4.19-4.31 (m, 2H), 4.01-4.13 (m, 1H).

Workup

  1. waitThe resulting solution was left
  2. customThe layers were separated
  3. extractionthe resulting aqueous layer was further extracted with diethyl ether (2×100 mL)
  4. washThe combined organics were then washed with water (100 mL), brine (100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-69738a0661b24021b631593c7d261dc7
Source dataset
uspto-grants-2014_09
Patent number
US08822456B2

Reaction notes

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