Benzyl Alcohol → Benzyl [2-(3-bromophenyl)propan-2-yl]carbamate

HRID 272650Notes

Reaction equation

HRID 272650 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([N:11]=[C:12]=[O:13])([CH3:10])[CH3:9])[CH:3]=1.[CH2:14]([OH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([NH:11][C:12](=[O:13])[O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([CH3:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 244Benzyl AlcoholHCID 21329846HCID 21329846, compound

Product 1

HCID 58641875Benzyl [2-(3-bromophenyl)propan-2-yl]carbamate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
100 °C

Procedure

To solution of A6.1c (11 g, 0.045 mol) in dichloromethane (110 ml) was added triethylamine (5.85 g, 0.057 mol) and cooled to 0° C. under N2. Ethylchloroformate (5.65 g, 0.05 mol) was added drop wise and stirred at 0° C. for 1 h. Sodium azide (3.24 g, 0.049 mol) was added and the mixture was stirred at RT over night. Reaction mixture was filtered to remove triethylamine-hydrochloride salt. The organic layer was concentrated to provide 1-azido-2-(3-bromophenyl)-2-methylpropan-1-one which was dissolved in toluene (60 mL) and heated to 100° C. for 30 min. The toluene was removed under vacuum to provide 1-bromo-3-(2-isocyanatopropan-2-yl)benzene. A mixture of 1-bromo-3-(2-isocyanatopropan-2-yl)benzene, pyridine (30 ml) and benzyl alcohol (12.2 g, 0.113 mol) was heated to 100° C. for 2 h under nitrogen. The reaction mixture was cooled to RT, quenched with 1.5 N HCl and extracted with ethyl acetate (3×50 ml). The combined organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated. Product was purified by column chromatography to give 7 g (45%) of A6.1d. 1H NMR (300 MHz, CDCl3) 1.65 (s, 6H), 5.03 (s, 2H), 5.1 (bs, 1H), 7.2 (dd, 1H), 7.35 (m, 6H), 7.54 (s, 1H). LCMS (M−H)+=350.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. customquenched with 1.5 N HCl
  3. extractionextracted with ethyl acetate (3×50 ml)
  4. washThe combined organic layer was washed with water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customProduct was purified by column chromatography
  8. customto give 7 g (45%) of A6.1d

Sources & evidence

ORD record
ord-dd667129248345ada71b37e3925d5e4b
Source dataset
uspto-grants-2008_11
Patent number
US07456194B2

Reaction notes

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