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

HRID 605238Notes

Reaction equation

HRID 605238 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)C(O)=O.C[N:12]1[CH2:17]COCC1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:25])C=CC=CC=1.[CH2:35]([OH:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>ClCCCl>[CH2:35]([O:42][C:17](=[O:25])[NH:12][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Br:1])[CH:10]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 79724-MethylmorpholineHCID 887075-Bromonicotinic acidHCID 199401P,P-Diphenylphosphinic azide

Product 1

HCID 18446849Benzyl (5-bromopyridin-3-yl)carbamateYield 34.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 5-bromonicotinic acid (1.00 g, 4.95 mmol) and N-methylmorpholine (0.60 mL, 5.445 mmol) in anhydrous 1,2-dichloroethane (20 mL) was stirred under a nitrogen atmosphere for 10 minutes at room temperature. Diphenyl phosphoryl azide (1.17 mL, 5.445 mmol) was then added dropwise and the reaction stirred for 30 minutes at the same temperature. The reaction was then slowly heated to 75° C. over a 20-minute period and was maintained at this temperature for 1 hour. Benzyl alcohol (0.77 mL, 7.434 mmol) and cuprous chloride (15 mg) were added and the reaction was refluxed for 3 hours. The reaction was then cooled to room temperature and the solvent removed by rotary evaporation in vacuo. Purification by silica gel chromatography eluting with a gradient of 12% and 20% ethyl acetate/methylene chloride afforded the title compound as a white solid (524 mg, 34%).

Workup

  1. stirringthe reaction stirred for 30 minutes at the same temperature
  2. temperatureThe reaction was then slowly heated to 75° C. over a 20-minute period
  3. temperaturewas maintained at this temperature for 1 hour
  4. temperaturethe reaction was refluxed for 3 hours
  5. temperatureThe reaction was then cooled to room temperature
  6. customthe solvent removed by rotary evaporation in vacuo
  7. customPurification by silica gel chromatography
  8. washeluting with a gradient of 12% and 20% ethyl acetate/methylene chloride

Sources & evidence

ORD record
ord-ec9bfdb3d8d44838b55825924e95caed
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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