Hydrochloric Acid → Boc-cyclohexylalanine

HRID 1604048Notes

Reaction equation

HRID 1604048 reaction equation
C1(NC2CCCCC2)CCCCC1.[C:14]([N:21]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C@H:22]([C:24]([OH:26])=[O:25])[CH3:23])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].Cl>C(OCC)(=O)C>[C:14]([N:21]([CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C@H:22]([C:24]([OH:26])=[O:25])[CH3:23])([O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 70189060Boc-Cyclohexylalanine Dicyclohexylamine salt

Product 1

HCID 18663859Boc-cyclohexylalanine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Boc-Cyclohexylalanine-Dicyclohexylamine salt (0.497 g, 1.1 mM) was added to a mixture of ethyl acetate (25 ml) and 0.5 N HCl (25 ml) for 30 minutes. The ethyl acetate layer was separated, washed with water (3×100 ml), dried over MgSO4, and evaporated to give the Boc-Cyclohexylalanine free acid (1.1 mM). The acid was dissolved in 25 ml of THF and cooled to 5° C. under N2. The acid was converted into a mixed anhydride by treatment with N-methyl morpholine (100 ul, 1 mM) and Isobutylchloroformate (130 ul, 1 mM). After stirring for 20 minutes, a solution of a racemic mixture of 2-(R)-3(S)-(1H-5-imidazoyl)-cyclopropylamine and 2-(S)-3(R)-(1H-5-imidazoyl)-cyclopropylamine (200 mgs, 1 mM) and triethylamine (284 u., 2 mM) in 2 ml of water was added. After 2 hours, the reaction mixture was portioned between ethyl acetate (50 ml) and water (50 ml), the ethyl acetate layer was washed with saturated sodium bicarbonate solution, water, then dried over sodium sulfate, filtered, and evaporated in vacuo to give the BOC protected amine of L-Cyclohexylalanine amide of 3(S)-(1H-5-imidazoyl)-2(R)-cyclopropylamine and its diasterisomer, the L-Cyclohexylalanine amide of 3(R)-(1H-5-imidazoyl)-2(S)-cyclopropylamine. The BOC group was deprotected by treating the crude amides directly with Trifluoroacetic acid (5 ml) for 30 minutes at r.t. The TFA was evaporated, and the residue triturated with ether to provide the ditrifluoroacetic acid salt and the diastereisomeric mixture of (1R,2R)trans-2-(S)-amino-3-(cyclohexyl-N-(2-imidazol-4-ylcyclopropyl)propanamide and (1S,2S)-trans-2-(S)-amino-3-cyclohexyl-N-(2-imidazol-4-ylcyclopropyl)propanamide (300 mgs). The diastereoisomers were separated using reverse phase HPLC.

Workup

  1. customThe ethyl acetate layer was separated
  2. washwashed with water (3×100 ml)
  3. dry with materialdried over MgSO4
  4. customevaporated

Sources & evidence

ORD record
ord-e56cb7a93151429dbf5f0c9f67e33ca0
Source dataset
uspto-grants-1999_11
Patent number
US05990317

Reaction notes

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