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

HRID 2409887Notes

Reaction equation

HRID 2409887 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

Participants

4

Reactant 2

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

Product 1

HCID 71233117tert-Butyl (1R,2R)-2-(1-(4-(oxazol-2-yl)phenyl)piperidin-3-ylamino)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 methane sulfonate (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 mixture was concentrated. The residue was diluted with EtOAc and washed with water. The remaining EtOAc organic layer was concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 50-100% EtOAc/Hex. Under these conditions, the two diastereomers separated and the desired diastereomer tert-butyl (1R,2R)-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 mixture was concentrated
  3. additionThe residue was diluted with EtOAc
  4. washwashed with water
  5. concentrationThe remaining EtOAc organic layer was concentrated
  6. customThe resulting residue was purified
  7. washeluting with a gradient of 50-100% EtOAc/Hex
  8. customUnder these conditions, the two diastereomers separated

Sources & evidence

ORD record
ord-16b5b6198041438d86e3da85a4181990
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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