Benzyl Alcohol → benzyl ((1R,2R)-2-methylcyclopropyl)carbamate

HRID 2091585Notes

Reaction equation

HRID 2091585 reaction equation
C[C@@H]1C[C@H]1[C:5]([N:7]=[N+]=[N-])=[O:6].[CH2:10]([OH:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:18]1([CH3:24])[CH:23]=[CH:22]C=CC=1>CN(C=O)C.CCOCC.[Cu]Cl>[CH3:24][C@@H:18]1[CH2:23][C@H:22]1[NH:7][C:5](=[O:6])[O:17][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 244Benzyl AlcoholHCID 1140TolueneHCID 86670212(1R,2R)-2-methylcyclopropanecarbonyl azide

Product 1

HCID 86670213benzyl ((1R,2R)-2-methylcyclopropyl)carbamateYield 57%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (1R,2R)-2-methylcyclopropanecarbonyl azide (1.80 g, 14.4 mmol) in toluene (100 mL) was heated to 90° C. for 1 h. After gas evolution had subsided, the solution was cannulated into a flask containing a slurry of benzyl alcohol (4.5 mL, 43.2 mmol) and copper(I) chloride (750 mg, 7.5 mmol) in DMF (100 mL). The reaction was maintained at room temperature for 1 h, then diluted with Et2O (200 mL) then washed with brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography over silica gel (20-30% EtOAc/hexane eluent) to provide benzyl ((1R,2R)-2-methylcyclopropyl)-carbamate (1.68 g, 57% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.27-7.46 (m, 5 H), 5.11 (br. s., 2H), 4.80-4.99 (m, 1H), 2.28 (d, J=3.0 Hz, 1H), 1.07 (d, J=5.5 Hz, 3H), 0.82-0.97 (m, 1H), 0.67 (ddd, J=9.0, 5.3, 3.8 Hz, 1H), 0.51 (q, J=5.9 Hz, 1H).

Workup

  1. customthe solution was cannulated into a flask
  2. washthen washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography over silica gel (20-30% EtOAc/hexane eluent)

Sources & evidence

ORD record
ord-6d09dfab11694574a6aa614ab3d454cb
Source dataset
uspto-grants-2013_05
Patent number
US08440652B2

Reaction notes

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