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

HRID 269471Notes

Reaction equation

HRID 269471 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 chromatography (15-50% EtOAc in Hexane) provided 22.2 g (72.5 mmol, 73% yield) of benzyl 5-bromo-3-pyridinylcarbamate: 1H NMR (CDCl3) δ 8.39-8.32 (m, 2 H), 8.29 (s, 1 H), 7.45-7.32 (m, 5 H), 6.94 (s, 1 H), 5.22 (s, 2 H); 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 chromatography (15-50% EtOAc in Hexane)

Sources & evidence

ORD record
ord-013b121e58f544ea96dcf6a49cf75122
Source dataset
uspto-grants-2008_11
Patent number
US07446204B2

Reaction notes

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