Dicyclohexylcarbodiimide → HCID 70003015, compound

HRID 1861629Notes

Reaction equation

HRID 1861629 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[NH:45]1[CH2:59][CH2:58][CH2:57][C@H:46]1[C:47]([O:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:48].Cl.C(N(CC)C(C)C)(C)C>ClCCl>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([N:45]1[CH2:59][CH2:58][CH2:57][C@H:46]1[C:47]([O:49][CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)=[O:48])=[O:12])[CH2:3][CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 2755927(2R)-2-{[(tert-butoxy)carbonyl]amino}-3-cyclohexylpropanoic acid

Product 1

HCID 70003015HCID 70003015, compoundYield 98.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 11.64 g of Boc-D-Cha-OH in 100 mL of dichloromethane at 0° C. was added 6.36 g of HOBt and 9.72 g of DCC. After 20 minutes a solution of 10.35 g of H-Pro-OBzl.HCl in 40 mL of dichloromethane adjusted with N,N-diisopropyl ethylamine to pH 8 was added. After 16 h the reaction mixture was filtered and the filtrate was washed successively with water, 0.1 N hydrochloric acid, water, aqueous 5% sodium hydrogencarbonate and brine. All aqueous washes were extracted twice with ethyl acetate, all organic extracts combined, dried over sodium sulfate and concentrated. To the residue was added a mixture of ethyl acetate/heptanes=1/1 (v/v), the resulting suspension filtered and the filtrate purified by chromatography on silica gel (eluent: ethyl acetate/heptanes=1/1 v/v) to yield 19.34 g of Boc-D-Cha-Pro-OBzl.

Workup

  1. additionwas added
  2. filtrationAfter 16 h the reaction mixture was filtered
  3. washthe filtrate was washed successively with water, 0.1 N hydrochloric acid, water, aqueous 5% sodium hydrogencarbonate and brine
  4. extractionAll aqueous washes were extracted twice with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. additionTo the residue was added
  8. additiona mixture of ethyl acetate/heptanes=1/1 (v/v)
  9. filtrationthe resulting suspension filtered
  10. customthe filtrate purified by chromatography on silica gel (eluent: ethyl acetate/heptanes=1/1 v/v)

Sources & evidence

ORD record
ord-ceb80e79f0d147419363846424da3e92
Source dataset
uspto-grants-2003_03
Patent number
US06534495B1

Reaction notes

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