Dichloromethane → HCID 86728136, compound

HRID 627675Notes

Reaction equation

HRID 627675 reaction equation
[CH2:1]([CH:4]1[C@:9]([C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[N:8]=[C:7]([N:21]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:6]([CH3:37])([CH3:36])[S:5]1(=[O:39])=[O:38])[CH:2]=C.C(=O)(O)[O-:41].[Na+].C(Cl)Cl.[BH4-].[Na+]>CO>[C:24]([O:23][C:22]([N:21]([C:7]1[C:6]([CH3:37])([CH3:36])[S:5](=[O:38])(=[O:39])[CH:4]([CH2:1][CH2:2][OH:41])[C@:9]([C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[N:8]=1)[C:29](=[O:30])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:28])([CH3:25])([CH3:26])[CH3:27]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 86728135HCID 86728135, compound

Product 1

HCID 86728136HCID 86728136, compoundYield 100.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 3-necked round bottom flask equipped with a mechanical stirrer, Claisen adapter with thermocouple and a nitrogen inlet was charged with tert-butyl N-[(3R)-2-allyl-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]-N-tert-butoxycarbonyl-carbamate (4.00 g, 7.02 mmol, 2.85:1 ratio of diastereomers), sodium bicarbonate (1.180 g, 14.04 mmol), DCM (30 mL) and MeOH (10.00 mL), and the resulting solution was cooled to Tinternal<−65+/−1° C. Ozone was bubbled through the reaction mixture until starting material was consumed according to LCMS (˜1.5 h). The solution was purged with oxygen and then nitrogen, and sodium borohydride (0.531 g, 14.04 mmol) added in one portion. The cooling bath was removed, and the reaction mixture was allowed to warm to RT overnight. 2 mL acetone was added, followed by 10 mL sat. aq.NH4Cl. After stirring for 10 min, 5 mL water was added and the layers were separated. The organic portion was dried over magnesium sulfate, filtered and concentrated in vacuo to provide tert-butyl N-tert-butoxycarbonyl-N-[(3R)-3-(2-fluoro-5-nitro-phenyl)-2-(2-hydroxyethyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (4.04 g, 2.85:1 ratio of diastereomers) as a white solid that was used without further purification. LC/MS (ESI+) m/z=596.2 (M+Na).

Workup

  1. customA 3-necked round bottom flask equipped with a mechanical stirrer
  2. temperaturethe resulting solution was cooled to Tinternal<−65+/−1° C
  3. customOzone was bubbled through the reaction mixture
  4. customwas consumed
  5. customaccording to LCMS (˜1.5 h)
  6. customThe solution was purged with oxygen
  7. customThe cooling bath was removed
  8. addition2 mL acetone was added
  9. addition5 mL water was added
  10. customthe layers were separated
  11. dry with materialThe organic portion was dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7206698f2f8048d79b407886c1878719
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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