Sodium hydride → ethyl 1-[(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methyl]-1H-pyrazole-4-carboxylate

HRID 217465Notes

Reaction equation

HRID 217465 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:5]=[N:4]1.[F:13][C:14]([F:41])([F:40])[C:15]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:16]=1[CH2:17][O:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[C:24]([CH2:29]Br)[CH2:25][O:26]2)=[C:21]([F:31])[CH:20]=1>CN(C=O)C>[F:41][C:14]([F:13])([F:40])[C:15]1[CH:35]=[C:34]([C:36]([F:37])([F:39])[F:38])[CH:33]=[CH:32][C:16]=1[CH2:17][O:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[C:24]([CH2:29][N:3]3[CH:7]=[C:6]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:5]=[N:4]3)[CH2:25][O:26]2)=[C:21]([F:31])[CH:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 866576487-{[2,4-bis(trifluoromethyl)benzyl]oxy}-3-(bromomethyl)-5-fluoro-2H-chromene

Product 1

HCID 86657650ethyl 1-[(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methyl]-1H-pyrazole-4-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methanol (200 mg) in MeCN (5 mL) was added triphenylphosphine dibromide (240 mg). The reaction liquid was stirred at room temperature for 2 hours and concentrated under reduced pressure. To the residue were added EtOAc and IPE, the resulting solid was removed by filtration, and the filtrate was concentrated to obtain 7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-3-(bromomethyl)-5-fluoro-2H-chromene (230 mg) as a brown liquid. 60% sodium hydride (24 mg) was added to a DMF solution (5 mL) at 0° C., and subsequently, ethyl 1H-pyrazole-4-carboxylate (76 mg) was added thereto. The mixture was stirred at room temperature for 0.5 hours, and a solution of 7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-3-(bromomethyl)-5-fluoro-2H-chromene (220 mg) in DMF (5 mL) was added thereto at 0° C. The reaction liquid was stirred at room temperature for 13 hours, quenched with a saturated NH4Cl solution, and then extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=100:0 to 70:30) to obtain ethyl 1-[(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methyl]-1H-pyrazole-4-carboxylate (111 mg) as a pale yellow solid.

Workup

  1. customat 0° C
  2. customThe reaction liquid
  3. stirringwas stirred at room temperature for 13 hours
  4. customquenched with a saturated NH4Cl solution
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:EtOAc=100:0 to 70:30)

Sources & evidence

ORD record
ord-cecbd34ebbfd42858f57887a3cd41ec5
Source dataset
uspto-grants-2012_06
Patent number
US08193378B2

Reaction notes

Loading…