Dichloromethane → N-[2-(4-Fluorophenyl)-1-(4-hydroxyphenyl)ethyl]formamide

HRID 1955799Notes

Reaction equation

HRID 1955799 reaction equation
C(Cl)Cl.C[O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([NH:21][CH:22]=[O:23])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[CH:8][CH:7]=1.B(Br)(Br)Br>CCCCCC>[OH:5][C:6]1[CH:7]=[CH:8][C:9]([CH:12]([NH:21][CH:22]=[O:23])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 25134Boron tribromide2×HCID 19073181HCID 19073181, compound

Product 1

HCID 19073174N-[2-(4-Fluorophenyl)-1-(4-hydroxyphenyl)ethyl]formamideYield 92.1%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a -20° C. CH2Cl2 (100 mL) solution of N-[1-(4-methoxyphenyl)-2-(4-fluorophenyl)ethyl]formamide (1.6 g, 5.86 mmol) (for preparation see step A of Example 48) was added 11 mL of 1N BBr3 in hexane. After warming to 0° C. and stirring for one hour, an additional 5 mL of BBr3 solution was added. After 40 minutes, the reaction was complete by HPLC analysis. The reaction was quenched upon transferal into a stirred 4° C. aqueous NaHCO3 solution and extracted with CH2Cl2 (3×). The organic phases were washed with pH 4 NaH2PO4, brine, dried over Na2SO4 and concentrated to yield 1.4 g of N-[1-(4-hydroxyphenyl)-2-(4-fluorophenyl)ethyl]formamide as a yellow solid. To a 50° C. DMF (10 mL) containing benzyl bromide (400 mg, 2.3 mmol) and N-[1-(4-hydroxyphenyl)-2-(4-fluorophenyl)ethyl]formamide (450 mg, 1.7 mmol) under N2 was added 60% NaH (200 mg, 5 mmol). After one hour the reaction was quenched with H2O, extracted with EtOAc (3×). The organic phases were washed with H2O (3×), brine, dried over Na2SO4 and concentrated to yield 1 g of crude product. Flash chromatography on silica gel using 1:1 EtOAc/hexane eluted 300 mg of N-[1-(4-phenylmethoxyphenyl)-2-(4-fluorophenyl)ethyl]formamide. A 1:1 ETOH/H2O solution (10 mL) containing N-[1-(4-phenylmethoxyphenyl)-2-(4-fluorophenyl)ethyl]formamide (300 mg, 0.86 mmol) and NaOH (200 mg, 5 mmol) was refluxed for 40 hours, diluted with H2O and extracted 3× with EtOAc. The organic phases were washed with H2O (3×), brine, dried over Na2SO4 and concentrated to yield 290 mg of α-(4-phenylmethoxyphenyl)-4-fluorobenzeneethanamine.

Workup

  1. customTo a -20° C
  2. waitAfter 40 minutes
  3. customThe reaction was quenched upon transferal into a stirred 4° C. aqueous NaHCO3 solution
  4. extractionextracted with CH2Cl2 (3×)
  5. washThe organic phases were washed with pH 4 NaH2PO4, brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-93e6e3191eae412cacd474a172f046f1
Source dataset
uspto-grants-1998_07
Patent number
US05776983

Reaction notes

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