1-Aminocyclohexanecarboxylic acid → 1-((Fmoc)amino)cyclohexanecarboxylic acid

HRID 1770103Notes

Reaction equation

HRID 1770103 reaction equation
[NH2:1][C:2]1([C:8]([OH:10])=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH:11]1[C:23]2[CH:22]([CH2:24][O:25][C:26](Cl)=[O:27])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1>O1CCOCC1>[CH:11]1[C:23]2[CH:22]([CH2:24][O:25][C:26]([NH:1][C:2]3([C:8]([OH:10])=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]3)=[O:27])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 13661-Aminocyclohexanecarboxylic acidHCID 343679-Fluorenylmethyl chloroformate

Product 1

HCID 27560931-((Fmoc)amino)cyclohexanecarboxylic acidYield 6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

To a chilled (ice bath) suspension of aminocyclohexanecarboxylic acid (2.51 g, 17.5 mmol) in alumina-filtered dioxane (17 mL) were added 10% Na2CO3 (35 mL) and a solution of 9-fluorenylmethylchloroformate (4.57 g, 17.7 mmol) in 26 mL of dioxane (added slowly). The reaction mixture was allowed to warm to about 20° C. and stirred overnight under N2. The reaction mixture was poured into ~300 mL of ice water and washed with anhydrous ether (some product went into the ether layer). The aqueous layer was chilled in an ice bath and acidified with concentrated hydrochloric acid to pH about 2. The aqueous layer was then extracted with ethyl acetate (3×100 mL). The combined ethyl acetate layers were washed with 0.1N HCl and H2O. The ether and ethyl acetate layers were dried over anhydrous MgSO4, combined and concentrated. The resulting compound was flash chromatographed with a gradient of 40-50% EtOAc/Hexane to yield 0.383 g (1.05 mmol, 6.0% yield) of the title compound as a white foam DEI M+@m/z=365.

Workup

  1. temperatureTo a chilled
  2. filtrationfiltered dioxane (17 mL)
  3. additionwere added 10% Na2CO3 (35 mL)
  4. washwashed with anhydrous ether (some product
  5. temperatureThe aqueous layer was chilled in an ice bath
  6. extractionThe aqueous layer was then extracted with ethyl acetate (3×100 mL)
  7. washThe combined ethyl acetate layers were washed with 0.1N HCl and H2O
  8. dry with materialThe ether and ethyl acetate layers were dried over anhydrous MgSO4
  9. concentrationconcentrated
  10. customchromatographed with a gradient of 40-50% EtOAc/Hexane

Sources & evidence

ORD record
ord-b328a9088259436aaa4463febbcfa306
Source dataset
uspto-grants-1995_01
Patent number
US05385910

Reaction notes

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