Methyl chloroformate → (1R,4R)-4-((Methoxycarbonyl)amino)cyclohexane-1-carboxylic acid

HRID 559305Notes

Reaction equation

HRID 559305 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH2:11])[CH2:7][CH2:6]1)=[O:4].CCN(CC)CC.[CH3:19][O:20][C:21](Cl)=[O:22]>C(Cl)Cl>[CH3:19][O:20][C:21]([NH:11][CH:8]1[CH2:9][CH2:10][CH:5]([C:3]([OH:2])=[O:4])[CH2:6][CH2:7]1)=[O:22]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 178501207HCID 178501207, compound

Product 1

HCID 58375509(1R,4R)-4-((Methoxycarbonyl)amino)cyclohexane-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of trans-4-amino-cyclohexanecarboxylic acid methyl ester (commercially available) in CH2Cl2 was added Et3N (2 eq.) and methyl-chloroformate (1.05 eq.). Stirring was continued overnight at RT. The reaction was quenched by addition of H2O, the product was extracted with CH2Cl2 and the organic phase washed with aq. HCl 1M. The combined organic phases were dried over Na2SO4 and concentrated under vacuo. The residue was dissolved in MeOH and a 2M KOH aq. solution was added. The reaction was stirred at RT 4 hours, aq. HCl was added until ph=6, and then the product was extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated under vacuo to afford the title product as a white foam which was used in the next step without further purification.

Workup

  1. customThe reaction was quenched by addition of H2O
  2. extractionthe product was extracted with CH2Cl2
  3. washthe organic phase washed with aq. HCl 1M
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated under vacuo
  6. dissolutionThe residue was dissolved in MeOH
  7. additiona 2M KOH aq. solution was added
  8. stirringThe reaction was stirred at RT 4 hours
  9. additionaq. HCl was added until ph=6
  10. extractionthe product was extracted with EtOAc
  11. dry with materialThe combined organic phases were dried over Na2SO4
  12. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-d5c5c6cafd074cccbcfccfd7ec2514fa
Source dataset
uspto-grants-2011_11
Patent number
US08063075B2

Reaction notes

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