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

HRID 1046261Notes

Reaction equation

HRID 1046261 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>[CH:13]1([N:11]2[CH:12]=[C:8]([C:31]3[CH:30]=[CH:29][C:28]([C@@H:26]([N:22]4[CH2:21][CH2:20][C@:19]([CH2:18][C:17]([OH:16])([CH3:49])[CH3:50])([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)[O:24][C:23]4=[O:25])[CH3:27])=[CH:33][CH:32]=3)[CH:9]=[N:10]2)[CH2:15][CH2:14]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 584853763-{(S)-1-[4-(1-Cyclopropyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

2 M aqueous Na2CO3 solution (0.37 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 (0.35 g) in dimethylformamide (3 mL). The resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (20 mg) was added. The mixture was heated to 90° C. and stirred at this temperature for 2 h. 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 chromatography on silica gel (tert-butyl methyl ether/dichloromethane/NH4OH 96:4:0.1->94:6:0.1) to afford the title compound as a solid. Yield: 0.18 g (55% of theory); Mass spectrum (ESI+): m/z=460 [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 (20 mg)
  2. additionwas added
  3. temperatureAfter cooling to ambient temperature
  4. additionwater was added
  5. extractionthe resulting mixture was extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (tert-butyl methyl ether/dichloromethane/NH4OH 96:4:0.1->94:6:0.1)

Sources & evidence

ORD record
ord-c8c9b9fd1821464fb5d5afd6c0d733fe
Source dataset
uspto-grants-2013_10
Patent number
US08569292B2

Reaction notes

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