Dicyclohexylamine → HCID 15028272, compound

HRID 1441189Notes

Reaction equation

HRID 1441189 reaction equation
[NH:1]([C:10]([O:12][CH2:13][CH:14]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])[C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH2:4][S:5][CH3:6].O[N:28]1[C:33](=[O:34])[CH2:32][CH2:31][C:29]1=[O:30].C1CCC(N=C=NC2CCCCC2)CC1.C1CCC(NC2CCCCC2)CC1>C1COCC1.C(OCC)(=O)C>[NH:1]([C:10]([O:12][CH2:13][CH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]2[C:26]1=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:11])[C@H:2]([C:7]([O:9][N:28]1[C:33](=[O:34])[CH2:32][CH2:31][C:29]1=[O:30])=[O:8])[CH2:3][CH2:4][S:5][CH3:6]

Participants

7

Reactant 4

HCID 7582DicyclohexylamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 2724632N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-L-methionine

Product 1

HCID 15028272HCID 15028272, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Fmoc-Met-OSu was prepared in situ by the reaction of Fmoc-Met-OH (14.87 g), HOSu (5.52 g) and DCC (8.26 g) in THF (tetrahydrofuran, 200 ml) at 0° C. for 3.5 hours. Precipitated dicyclohexylurea (DCU) was removed by filtration and the THF filtrate was added to a cold solution of H-Asp(OtBu)-OH in 220 ml of 10:1 water/THF to which had been added 40 ml of 1N sodium hydroxide. After stirring the reaction mixture at room temperature overnight, solid citric acid (20 g) was added along with ethyl acetate (600 ml). The ethyl acetate layer was separated, washed with 10% citric acid and brine, then dried (MgSO4). Evaporation of the ethyl acetate solution gave a residue which was dissolved in ethyl acetate (200 ml) and treated with DCHA (7.84 ml) to precipitate 17.93 g of the DCHA salt of the title compound, mp 159°-162° C.

Workup

  1. customPrecipitated dicyclohexylurea (DCU) was removed by filtration
  2. additionthe THF filtrate was added to a cold solution of H-Asp(OtBu)-OH in 220 ml of 10:1 water/THF to which
  3. additionhad been added 40 ml of 1N sodium hydroxide
  4. additionwas added along with ethyl acetate (600 ml)
  5. customThe ethyl acetate layer was separated
  6. washwashed with 10% citric acid and brine
  7. dry with materialdried (MgSO4)
  8. customEvaporation of the ethyl acetate solution
  9. customgave a residue which
  10. customto precipitate 17.93 g of the DCHA salt of the title compound, mp 159°-162° C.

Sources & evidence

ORD record
ord-0d219f31ee02419c8bee6a7b2f29648c
Source dataset
uspto-grants-1996_03
Patent number
US05502164

Reaction notes

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