Benzyl Bromide → HCID 22261167, compound

HRID 898428Notes

Reaction equation

HRID 898428 reaction equation
[C:1]1([C:7]2[O:8][CH:9]=[C:10]([CH2:12][CH2:13][OH:14])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:17]([O:14][CH2:13][CH2:12][C:10]1[N:11]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 10487882HCID 10487882, compound

Product 1

HCID 22261167HCID 22261167, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(2-phenyloxazol-4-yl)-ethanol (Eli Lilly and Co. WO 9613264) (500 mg, 2.64 mmol) in THF (8 mL) was added NaH (215 mg, 5.28 mmol), followed by tetrabutylammonium iodide (96 mg, 0.26 mmol). After 10 min, benzyl bromide (677 mg, 3.96 mmol, 0.47 mL) was added via syringe. After 3 h, the reaction was partitioned between H2O (20 mL) and diethyl ether (20 mL). The organic phase was washed with brine and then the combined aqueous phases were back extracted with ether (50 mL). The organic phases were dried (MgSO4), filtered and concentrated. The product was purified by flash chromatography (80 mL SiO2, 25% EtOAc/hexanes) and obtained as a colorless oil (690 mg, 93%): Rf=0.46 in 25% EtOAc/hexanes; 1H NMR (500 MHz, CDCl3) δ 8.03-8.01 (m, 2H), 7.52 (t, J=1.0 Hz, 1H), 7.45-7.41 (m, 3H), 7.34-7.33 (m, 3H), 7.29-7.26 (m, 1H), 4.57 (s, 2H), 3.80 (t, J=7.0 Hz, 2H), 2.93 (t, J=7.0 Hz, 2H); 13C (125 MHz, CDCl3) δ 161.3, 139.3, 138.2, 135.0, 130.1, 128.7, 128.4, 127.7, 127.6, 126.3, 73.0, 68.5, 27.3.

Workup

  1. waitAfter 3 h
  2. customthe reaction was partitioned between H2O (20 mL) and diethyl ether (20 mL)
  3. washThe organic phase was washed with brine
  4. extractionthe combined aqueous phases were back extracted with ether (50 mL)
  5. dry with materialThe organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by flash chromatography (80 mL SiO2, 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-316533c56892428fba45042aa6ab3af8
Source dataset
uspto-grants-2008_04
Patent number
US07351728B2

Reaction notes

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