Triphenylphosphane dibromide → 7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-3-(bromomethyl)-5-fluoro-2H-chromene

HRID 217464Notes

Reaction equation

HRID 217464 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:4]=1[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17]O)[CH2:13][O:14]2)=[C:9]([F:19])[CH:8]=1.[Br-:30].[Br-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC#N>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:4]=1[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][Br:30])[CH2:13][O:14]2)=[C:9]([F:19])[CH:8]=1

Participants

4

Reactant 2

HCID 12890784Triphenylphosphane dibromideHCID 86657649(7-{[2,4-bis(trifluoromethyl)benzyl]oxy}-5-fluoro-2H-chromen-3-yl)methanol

Product 1

HCID 866576487-{[2,4-bis(trifluoromethyl)benzyl]oxy}-3-(bromomethyl)-5-fluoro-2H-chromeneYield 100.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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. customThe reaction liquid
  2. concentrationconcentrated under reduced pressure
  3. additionTo the residue were added EtOAc and IPE
  4. customthe resulting solid was removed by filtration
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-31a4eded0fd74726aaf8b4125ab7369e
Source dataset
uspto-grants-2012_06
Patent number
US08193378B2

Reaction notes

Loading…