(1R,2R)-trans-N-Boc-1,2-cyclohexanediamine → tert-Butyl (1R,2R)-2-(1-(4-(oxazol-2-yl)phenyl)piperidin-3-ylamino)cyclohexylcarbamate

HRID 2369985Notes

Reaction equation

HRID 2369985 reaction equation
CS(O[CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[O:19][CH:20]=[CH:21][N:22]=3)=[CH:14][CH:13]=2)[CH2:7]1)(=O)=O.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>C(#N)C>[O:19]1[CH:20]=[CH:21][N:22]=[C:18]1[C:15]1[CH:16]=[CH:17][C:12]([N:8]2[CH2:9][CH2:10][CH2:11][CH:6]([NH:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]3[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:7]2)=[CH:13][CH:14]=1.[O:19]1[CH:20]=[CH:21][N:22]=[C:18]1[C:15]1[CH:14]=[CH:13][C:12]([N:8]2[CH2:9][CH2:10][CH2:11][CH:6]2[CH2:7][NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:17][CH:16]=1

Participants

5

Reactant 2

HCID 1514390(1R,2R)-trans-N-Boc-1,2-cyclohexanediamineHCID 866902081-(4-(Oxazol-2-yl)phenyl)piperidin-3-yl methanesulfonate

Product 2

HCID 71233117tert-Butyl (1R,2R)-2-(1-(4-(oxazol-2-yl)phenyl)piperidin-3-ylamino)cyclohexylcarbamateHCID 86690209tert-butyl (1R,2R)-2-((1-(4-(oxazol-2-yl)phenyl)pyrrolidin-2-yl)methylamino)cyclohexylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-(4-(oxazol-2-yl)phenyl)piperidin-3-yl methanesulfonate (110 mg, 0.341 mmol) in acetonitrile (4 mL) was added tert-butyl (1R,2R)-2-aminocyclohexylcarbamate (110 mg, 0.512 mmol). The reaction was stirred in a microwave at 120° C. for 30 min. After this time, LC/MS showed two pairs of products formed. The reaction was concentrated. The residue was diluted with EtOAc and washed with water. EtOAc extracts were concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 50-100% EtOAc/Hex to give desired product tert-butyl (1R,2R)-2-((1-(4-(oxazol-2-yl)phenyl)pyrrolidin-2-yl)methylamino)cyclohexylcarbamate and the unwanted diastereomer, tert-butyl (1R,2S)-2-((1-(4-(oxazol-2-yl)phenyl)pyrrolidin-2-yl)methylamino)cyclohexylcarbamate (156 mg total) as a white foam.

Workup

  1. customformed
  2. concentrationThe reaction was concentrated
  3. additionThe residue was diluted with EtOAc
  4. washwashed with water
  5. concentrationEtOAc extracts were concentrated
  6. customThe resulting residue was purified
  7. washeluting with a gradient of 50-100% EtOAc/Hex

Sources & evidence

ORD record
ord-bc1c982a2d2e4b53993fcc6b498a2c4d
Source dataset
uspto-grants-2014_04
Patent number
US08710049B2

Reaction notes

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