Benzyl Alcohol → Benzyl (5-bromopyridin-3-yl)carbamate

HRID 2054166Notes

Reaction equation

HRID 2054166 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:18])C=CC=CC=1.CC[N:30]([CH2:33]C)CC.[CH2:35]([OH:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:10]=[C:6]([NH:30][C:33](=[O:18])[O:42][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:5]=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 887075-Bromonicotinic acidHCID 199401P,P-Diphenylphosphinic azide

Product 1

HCID 18446849Benzyl (5-bromopyridin-3-yl)carbamateYield 73.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 5-bromonicotinic acid (20.0 g, 99.0 mmol) in toluene (200 mL) was added diphenylphosphoryl azide (25.6 mL, 118.8 mmol) and Et3N (16.6 mL, 118.8 mmol). After stirring at room temperature for 30 min, benzyl alcohol (15.4 mL, 148.5 mmol) was added. The mixture was stirred at room temperature for 1 h then refluxed overnight. After cooling to room temperature, the reaction mixture was washed with H2O, saturated aqueous NaHCO3 and brine, dried over MgSO4 and concentrated. Purification by flash column chromatography (eluent: 15-50% EtOAc in Hexane) provided benzyl 5-bromo-3-pyridinylcarbamate (22.2 g, 72.5 mmol, 73% yield): 1H NMR (CDCl3) δ 8.39-8.32 (m, 2H), 8.29 (s, 1H), 7.45-7.32 (m, 5H), 6.94 (s, 1H), 5.22 (s, 2H); ESMS m/e: 307.0 (M+H)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. temperaturethen refluxed overnight
  3. temperatureAfter cooling to room temperature
  4. washthe reaction mixture was washed with H2O, saturated aqueous NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (eluent: 15-50% EtOAc in Hexane)

Sources & evidence

ORD record
ord-9f020c78eef6487496cd0c782613db19
Source dataset
uspto-grants-2008_02
Patent number
US07329656B2

Reaction notes

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