Benzyl Alcohol → 1-(Benzyloxy)-3-bromo-5-fluorobenzene
Reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN(C=O)C.[Br:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19](F)[CH:18]=1>C1COCC1>[CH2:3]([O:10][C:19]1[CH:18]=[C:17]([Br:16])[CH:22]=[C:21]([F:23])[CH:20]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1Participants
Procedure
Sodium hydride (80% oil dispersion, 6.0 g, 201 mmol) was added slowly to a solution of benzyl alcohol (16 mL, 155 mmol) in THF (310 mL) at 0° C. DMF (300 mL) was added slowly and the reaction mixture was stirred until all of the NaH dissolved and gas evolution ceased. A solution of 1-bromo-3,5-difluorobenzene (30 g, 155 mmol) in THF (30 mL) was added and the reaction mixture was stirred for 30 min at ambient temperature. The reaction was quenched with saturated aqueous NH4Cl, and the reaction mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with saturated aqueous NH4Cl and brine, dried over MgSO4, filtered, and concentrated in vacuo to give a yellow liquid. 3-benzyloxy-5-fluorobromobenzene (28 g) was isolated by chromatography on silica gel (5% ethyl acetate, hexanes). Step 2. 4-[(3-benzyloxy-5-fluorophen-1-yl)oxomethyl]tetrahydropyran.
Workup
- dissolutiondissolved
- customThe reaction was quenched with saturated aqueous NH4Cl
- extractionthe reaction mixture was extracted 3 times with ethyl acetate
- washThe combined organic layers were washed with saturated aqueous NH4Cl and brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customto give a yellow liquid
Sources & evidence
- ORD record
- ord-a3f481ad2af04572b91fa6b849b568e7
- Source dataset
- uspto-grants-1994_10
- Patent number
- US05354865
Reaction notes
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