Sodium hydride → HCID 86701731, compound

HRID 2174095Notes

Reaction equation

HRID 2174095 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4C(OC(C)(C)C)=O)([OH:16])[C:12]([F:15])([F:14])[F:13])=[N:8][C:7]=2[CH:36]=1)#[N:2].[H-].[Na+].C[O:40][C:41](=[O:47])[C:42]([CH3:46])([CH3:45])[CH2:43]Br.C[Si](C)(C)[O-].[K+]>CN(C=O)C.CCOC(C)=O.C1COCC1.Cl.[Cl-].[Na+].O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)([O:16][CH2:43][C:42]([CH3:46])([CH3:45])[C:41]([OH:47])=[O:40])[C:12]([F:15])([F:13])[F:14])=[N:8][C:7]=2[CH:36]=1)#[N:2]

Participants

10

Reactant 4

HCID 24758Sodium hydrideHCID 19604604methyl 3-bromo-2,2-dimethylpropanoateHCID 23668039Potassium trimethylsilanolate2×HCID 86701717HCID 86701717, compound

Product 1

HCID 86701731HCID 86701731, compound

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of (±)-2-(2,2,2-trifluoro-1-hydroxy-1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)benzo[d]oxazole-5-carbonitrile (Example 128-A) (50 mg, 0.100 mmol) in DMF (0.3 ml), NaH (oil dispersion, 60%) (11.96 mg, 0.299 mmol) was added at rt under nitrogen. After stirring for 15 min., 3-bromo-2,2-dimethylpropionic acid methyl ester (0.043 ml, 0.299 mmol; CAS#30452-00-7) was added at the same temperature. The mixture was warmed up to 90° C. After stirring for 2 h, the mixture was cooled to rt and diluted with EtOAc and 1M NaHSO4aq. The organic layer was separated, dried over Na2SO4, filtered, and concentrated. To a solution of the resulting residue in THF (0.5 ml), potassium trimethylsilanolate (38.5 mg, 0.300 mmol) was added at rt under nitrogen. After stirring for 19 h, additional THF (0.5 ml) and potassium trimethylsilanolate were added. The mixture was heated at 50° C. for 1 h, and then the mixture was cooled to rt. The mixture was diluted with EtOAc, 1M HCl aq. and brine. The layers were separated and the aqueous layer extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The crude was purified by RP-HPLC (HC-A) to give the title compound as a 0.25-TFA salt.

Workup

  1. additionwas added at rt under nitrogen
  2. stirringAfter stirring for 2 h
  3. temperaturethe mixture was cooled to rt
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringAfter stirring for 19 h
  9. temperatureThe mixture was heated at 50° C. for 1 h
  10. temperaturethe mixture was cooled to rt
  11. customThe layers were separated
  12. extractionthe aqueous layer extracted twice with EtOAc
  13. washThe combined organic layer was washed with brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude was purified by RP-HPLC (HC-A)

Sources & evidence

ORD record
ord-7910a6b59cd048a8a617469416614425
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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