Benzyl Alcohol → (1S,3R)-1-(Boc-amino)-3-(Cbz-amino)cyclopentane

HRID 1257635Notes

Reaction equation

HRID 1257635 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:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>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:48][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:24])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 1512526(1R,3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acid

Product 1

HCID 67351544(1S,3R)-1-(Boc-amino)-3-(Cbz-amino)cyclopentaneYield 43.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (1R,3S)-3-tert-butoxycarbonylamino-cyclopentanecarboxylic acid (1.0 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 3 hours then cooled to ambient temperature. Benzyl alcohol (2.48 mL, 23.98 mmol) and DMAP (54 mg, 0.44 mmol) were added and the resulting mixture heated at 90° C. for 16 hours. The cooled reaction mixture was concentrated under vacuum and the resulting residue was dissolved in ethyl acetate. The organic layer was washed with 10% aqueous citric acid and brine and the organic layer dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane) to afford 635 mg (43%) of ((1S,3R)-3-benzyloxycarbonylamino-cyclopentyl)-carbamic acid tert-butyl ester. 1H NMR (400 MHz, DMSO) δ: 7.36 (m, 5H), 6.84 (d, 1H), 5.00 (s, 2H), 3.78 (m, 2H), 2.14 (m, 1H), 1.76 (m, 2H), 1.53-1.43 (m, 2H), 1.37 (s, 9H), 1.32-1.20 (m, 1H).

Workup

  1. temperaturethen cooled to ambient temperature
  2. temperaturethe resulting mixture heated at 90° C. for 16 hours
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated under vacuum
  5. dissolutionthe resulting residue was dissolved in ethyl acetate
  6. washThe organic layer was washed with 10% aqueous citric acid and brine
  7. dry with materialthe organic layer dried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-a6be07b65d894fc38a04ce89394a8641
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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