Sodium Carbonate → (S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-isopropyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one

HRID 1046260Notes

Reaction equation

HRID 1046260 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[N:10][N:11]([CH:13]([CH3:15])[CH3:14])[CH:12]=1.[OH:16][C:17]([CH3:50])([CH3:49])[CH2:18][C@@:19]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:24][C:23](=[O:25])[N:22]([C@H:26]([C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)[CH3:27])[CH2:21][CH2:20]1>CN(C)C=O>[OH:16][C:17]([CH3:49])([CH3:50])[CH2:18][C@@:19]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:24][C:23](=[O:25])[N:22]([C@H:26]([C:28]2[CH:29]=[CH:30][C:31]([C:8]3[CH:9]=[N:10][N:11]([CH:13]([CH3:15])[CH3:14])[CH:12]=3)=[CH:32][CH:33]=2)[CH3:27])[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 223292004-Bromo-1-isopropyl-1H-pyrazoleHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 58485319(S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-isopropyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

2 M aqueous Na2CO3 solution (0.75 mL) was added to a solution of 4-bromo-1-isopropyl-1H-pyrazole (0.15 g) and (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-[(S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl]-1,3-oxazinan-2-one (0.25 g) in dimethylformamide (2 mL). The resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg) was added. The mixture was heated to 90° C. and stirred at this temperature for 6 h. Then another portion of [1,1′-bis(diphenyl-phosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg) was added and the mixture was further stirred at 100° C. overnight. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated. The residue was purified by HPLC on reversed phase (acetonitrile/water) followed by chromatography on silica gel (tert-butyl methyl ether/dichloromethane/NH4OH 95:5:0.1) to afford the title compound as a solid. Yield: 23 mg (9% of theory); Mass spectrum (ESI+): m/z=462 [M+H]+.

Workup

  1. customThe resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg)
  2. additionwas added
  3. additionThen another portion of [1,1′-bis(diphenyl-phosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg) was added
  4. stirringthe mixture was further stirred at 100° C. overnight
  5. temperatureAfter cooling to ambient temperature
  6. additionwater was added
  7. extractionthe resulting mixture was extracted with ethyl acetate
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was purified by HPLC on reversed phase (acetonitrile/water)

Sources & evidence

ORD record
ord-a5654ffe179944fb843827691b45000a
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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