Sodium Bicarbonate → HCID 86728117, compound

HRID 627650Notes

Reaction equation

HRID 627650 reaction equation
[CH2:1]([CH:4]1[S:9](=[O:11])(=[O:10])[C:8]([CH3:13])([CH3:12])[C:7]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:6][C@@:5]1([C:23]1[C:24]([F:30])=[N:25][CH:26]=[C:27]([Br:29])[CH:28]=1)[CH3:22])[CH:2]=C.C(=O)(O)[O-:32].[Na+].[BH4-].[Na+]>CO.C(Cl)Cl>[Br:29][C:27]1[CH:28]=[C:23]([C@:5]2([CH3:22])[CH:4]([CH2:1][CH2:2][OH:32])[S:9](=[O:11])(=[O:10])[C:8]([CH3:12])([CH3:13])[C:7]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[N:6]2)[C:24]([F:30])=[N:25][CH:26]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 86728118HCID 86728118, compound

Product 1

HCID 86728117HCID 86728117, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl ((5R)-6-allyl-5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.988 g, 1.96 mmol) in MeOH (5 mL) and DCM (15 mL) at room temperature was added sodium bicarbonate (0.333 g, 3.96 mmol). The reaction mixture was cooled to −78° C. and ozone was bubbled through the solution. After 15 min, the solution turned blue and oxygen was bubbled through the mixture for 5 min. Sodium borohydride (0.154 g, 4.07 mmol) was added and the reaction mixture was removed from the −78° C. bath. The solution was warmed to room temperature, stirred for 1 h, and quenched with saturated NH4Cl, and diluted with EtOAc water. The aqueous phase was extracted with EtOAc (2×). The combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, concentrated. Purification by flash column chromatography on silica gel (40 g, 20% to 60% EtOAc in hexanes) gave tert-butyl ((5R)-5-(5-bromo-2-fluoropyridin-3-yl)-6-(2-hydroxyethyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.913 g, 1.80 mmol, 92% yield) as a mixture of isomers that was used in the next step without separation. LC/MS (ESI+) m/z=508 (M+H).

Workup

  1. customozone was bubbled through the solution
  2. customoxygen was bubbled through the mixture for 5 min
  3. customthe reaction mixture was removed from the −78° C. bath
  4. temperatureThe solution was warmed to room temperature
  5. customquenched with saturated NH4Cl
  6. additiondiluted with EtOAc water
  7. extractionThe aqueous phase was extracted with EtOAc (2×)
  8. washThe combined organic extracts were washed with brine (1×)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash column chromatography on silica gel (40 g, 20% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3eb7a90caacd4dc88a328bbffefebefd
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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