Methanol → (3S)-3-[[6,6-dimethyl-5-(4-methylphenyl)-4,4-dioxo-5H-1,4,3-oxathiazin-2-yl]amino]-3-phenylpropan-1-ol

HRID 339833Notes

Reaction equation

HRID 339833 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@H:11]([NH:18][C:19]1[O:20][C:21]([CH3:42])([CH3:41])[CH:22]([C:27]2[CH:32]=[CH:31][C:30](OS(C(F)(F)F)(=O)=O)=[CH:29][CH:28]=2)[S:23](=[O:26])(=[O:25])[N:24]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(C(C)(C)C)(C)C.[CH3:43][Al](C)C.CO>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[CH3:41][C:21]1([CH3:42])[O:20][C:19]([NH:18][C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:10][CH2:9][OH:8])=[N:24][S:23](=[O:26])(=[O:25])[CH:22]1[C:27]1[CH:32]=[CH:31][C:30]([CH3:43])=[CH:29][CH:28]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 16682925TrimethylaluminumHCID 178431692HCID 178431692, compound

Product 1

HCID 178423786(3S)-3-[[6,6-dimethyl-5-(4-methylphenyl)-4,4-dioxo-5H-1,4,3-oxathiazin-2-yl]amino]-3-phenylpropan-1-ol

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 12024214Ditert-butyl(cyclopenta-1,3-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 1140TolueneSolvent

Procedure

Under inert gas, 60 mg of trifluoromethanesulfonic acid 4-{2-[(S)-3-(tert-butyldimethylsilanyloxy)-1-phenylpropylamino]-6,6-dimethyl-4,4-dioxo-5,6-dihydro-4H-4lambda6-1,4,3-oxathiazin-5-yl}phenyl ester, 5.3 mg of bis(dibenzylideneacetone)palladium and 13.1 mg of 1,2,3,4,5-pentaphenyl-1-(di-tert-butylphosphino)ferrocene were initially charged, dissolved in 1.2 ml of toluene and stirred at room temperature for 5 minutes. After the addition of 0.09 ml of a 2 N solution of trimethylaluminum, the reaction mixture was stirred at 80° C. for 2 hours. After cooling to room temperature, 1 ml of methanol was added and the solvent was removed under reduced pressure. The residue was dissolved in 2 ml of methanol, 0.2 ml of concentrated hydrochloric acid was added and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with 20 ml of ethyl acetate and 10 ml of water, and neutralized with sodium hydroxide solution. The organic phase was washed once again with saturated aqueous sodium chloride solution, dried over MgSO4 and concentrated by rotary evaporation. The residue was purified in a purification laboratory by means of preparative HPLC. The product-containing fractions were combined, the acetonitrile was removed under reduced pressure, and the aqueous residue was basified with saturated aqueous sodium hydrogencarbonate solution and extracted with dichloromethane. The organic phase was dried over MgSO4 and concentrated by rotary evaporation, and the residue was taken up again in a mixture of acetonitrile and water and lyophilized. This gave the product (22.8 mg) with a molecular weight of 402.5 g/mol (C21H26N2O4S); MS (ESI): m/e=403 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at 80° C. for 2 hours
  2. temperatureAfter cooling to room temperature
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in 2 ml of methanol
  5. addition0.2 ml of concentrated hydrochloric acid was added
  6. stirringthe mixture was stirred at room temperature for 1 hour
  7. additionThe reaction solution was diluted with 20 ml of ethyl acetate and 10 ml of water
  8. washThe organic phase was washed once again with saturated aqueous sodium chloride solution
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated by rotary evaporation
  11. customThe residue was purified in a purification laboratory by means of preparative HPLC
  12. customthe acetonitrile was removed under reduced pressure
  13. extractionextracted with dichloromethane
  14. dry with materialThe organic phase was dried over MgSO4
  15. concentrationconcentrated by rotary evaporation
  16. additionthe residue was taken up again in a mixture of acetonitrile and water

Sources & evidence

ORD record
ord-7443b49536354b039a525b3e74a842bc
Source dataset
uspto-grants-2014_11
Patent number
US08895547B2

Reaction notes

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