Benzyl Alcohol → benzyl N-(5-fluoropyridin-3-yl)carbamate

HRID 605229Notes

Reaction equation

HRID 605229 reaction equation
[F: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]([F: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 1202325-Fluoronicotinic AcidHCID 199401P,P-Diphenylphosphinic azide

Product 1

HCID 67040543benzyl N-(5-fluoropyridin-3-yl)carbamateYield 41.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
75 °C

Procedure

The product of Example 224A (1.00 g, 7.087 mmol) and N-methylmorpholine (0.86 mL, 7.796 mmol) in anhydrous 1,2-dichloroethane (30 mL) was stirred under a nitrogen atmosphere for 10 minutes at room temperature. Diphenyl phosphoryl azide (1.68 mL, 7.796 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 (1.10 mL, 10.63 mmol) and cuprous chloride (20 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 20% ethyl acetate/methylene chloride afforded the title compound as an off-white solid (718 mg, 41%).

Workup

  1. temperaturewas maintained at this temperature for 1 hour
  2. temperaturethe reaction was refluxed for 3 hours
  3. temperatureThe reaction was then cooled to room temperature
  4. customthe solvent removed by rotary evaporation in vacuo
  5. customPurification by silica gel chromatography
  6. washeluting with 20% ethyl acetate/methylene chloride

Sources & evidence

ORD record
ord-d7bb8e3937c742dca15beb8cbceaaa2d
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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