Citric Acid → (R)-2-(2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid cyclohexylamine salt

HRID 353393Notes

Reaction equation

HRID 353393 reaction equation
[CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8]([O:12][C:13](=[O:28])[CH2:14][C@@H:15]([CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]([OH:18])=[O:17])([CH3:11])([CH3:10])[CH3:9].C(OCC)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C1(N)CCCCC1>CO>[CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8]([O:12][C:13](=[O:28])[CH2:14][C@@H:15]([CH2:19][CH2:20][CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1)[C:16]([OH:18])=[O:17])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 7965CyclohexylamineHCID 8857Ethyl AcetateHCID 69431039HCID 69431039, compound

Product 1

HCID 69430977(R)-2-(2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid cyclohexylamine saltYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
22.5 °C

Procedure

(R)-2-[2-(tert-Butoxy)-2-oxoethyl]-5-phenylpentanoic acid cyclohexylamine salt (691 g, 1.77 mol) and ethyl acetate (7.0 liters) were added to an aqueous solution of citric acid (10%, 6.3 liters) and the organic phase was separated, washed with water (7.0 liters) and concentrated in vacuo to a yellow oil. A solution of the oil and 5% rhodium on carbon (51.6 g) in methanol (7.0 liters) was stirred at 20-25° C., under hydrogen (10 atmospheres, 150 p.s.i.) for 48 hours and then filtered through celite. To the filtrate was added cyclohexylamine (202 ml, 1.77 mol) and the methanol solution was stripped and replaced with methylethyl ketone by distillation at atmospheric pressure, to a volume of 5.5 liters. The mixture was allowed to cool to 20-25° C. where it was stirred for 48 hours and then filtered. The residue was washed with methylethyl ketone (2×500 ml) and then dried in vacuo at 45° C. for 4 hours to leave the title compound as a colourless solid (495 g, 71% yield, 99% pure by HPLC).

Workup

  1. customthe organic phase was separated
  2. washwashed with water (7.0 liters)
  3. concentrationconcentrated in vacuo to a yellow oil
  4. filtrationfiltered through celite
  5. distillationreplaced with methylethyl ketone by distillation at atmospheric pressure, to a volume of 5.5 liters
  6. temperatureto cool to 20-25° C. where it
  7. stirringwas stirred for 48 hours
  8. filtrationfiltered
  9. washThe residue was washed with methylethyl ketone (2×500 ml)
  10. customdried in vacuo at 45° C. for 4 hours

Sources & evidence

ORD record
ord-15ae6d9a61c9432ba315af299c8dc992
Source dataset
uspto-grants-2004_06
Patent number
US06750363B2

Reaction notes

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