Allyl Alcohol → ((1R,3R)-3-allyloxycarbonylamino-cyclopentyl)-carbamic acid tert-butyl ester

HRID 1257632Notes

Reaction equation

HRID 1257632 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@@H:11](C(O)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:24])C=CC=CC=1.C([N:36]([CH2:39]C)CC)C.[CH2:41]([OH:44])[CH:42]=[CH2:43]>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:13][CH2:12][C@@H:11]([NH:36][C:39]([O:44][CH2:41][CH:42]=[CH2:43])=[O:24])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 7858Allyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 1512527(1R,3R)-3-((tert-Butoxycarbonyl)amino)cyclopentanecarboxylic acid

Product 1

HCID 67352799((1R,3R)-3-allyloxycarbonylamino-cyclopentyl)-carbamic acid tert-butyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (1R,3R)-3-tert-butoxycarbonylamino-cyclopentanecarboxylic acid (1.00 g, 4.36 mmol), diphenylphosphoryl azide (1.41 mL, 6.54 mmol) and triethylamine (1.21 mL, 8.72 mmol) in toluene (15 mL) was heated at 90° C. for 2 hours then cooled to ambient temperature. Allyl alcohol (1.63 mL, 24.0 mmol) and DMAP (54.0 mg, 0.44 mmol) were added and the resulting mixture heated at 90° C. for 18 hours. The cooled reaction mixture was concentrated under vacuum and the resulting residue was dissolved in ethyl acetate. The mixture was washed with 10% aqueous citric acid, saturated aqueous sodium carbonate and brine and the combined aqueous layers were back-extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 12% ethyl acetate in cyclohexane) to afford 890 mg (72%) of ((1R,3R)-3-allyloxycarbonylamino-cyclopentyl)-carbamic acid tert-butyl ester. 1H NMR (400 MHz, DMSO) δ: 7.23 (d, 1H), 6.85 (d, 1H), 5.90 (m, 1H), 5.26 (dq, 1H), 5.16 (dq, 1H), 4.46-4.41 (m, 2H), 3.93-3.83 (m, 2H), 1.88 (m, 2H), 1.65 (t, 2H), 1.37 (s, 9H).

Workup

  1. temperaturethen cooled to ambient temperature
  2. temperaturethe resulting mixture heated at 90° C. for 18 hours
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated under vacuum
  5. dissolutionthe resulting residue was dissolved in ethyl acetate
  6. washThe mixture was washed with 10% aqueous citric acid, saturated aqueous sodium carbonate and brine
  7. extractionthe combined aqueous layers were back-extracted with ethyl acetate
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 12% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-9d9d13c6623f4787a2fabf95524d5a73
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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