Ethylmorpholine → HCID 178456004, compound

HRID 1655709Notes

Reaction equation

HRID 1655709 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:20][C@@H:21]([CH2:42][C:43]1[N:44]=[CH:45][NH:46][CH:47]=1)[C:22]([NH:24][C@@H:25]([CH2:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[C@@H:26]([OH:34])[CH2:27][C@@H:28]([CH:31]([CH3:33])[CH3:32])[CH:29]=[CH2:30])=[O:23].C(N1CCOCC1)C.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C)C=O>[CH:36]1([CH2:35][C@H:25]([NH:24][C:22]([C@@H:21]([NH:20][C:17]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:19])[CH2:42][C:43]2[N:44]=[CH:45][NH:46][CH:47]=2)=[O:23])[C@@H:26]([OH:34])[CH2:27][C@@H:28]([CH:31]([CH3:33])[CH3:32])[CH:29]=[CH2:30])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]1

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 178456019HCID 178456019, compound

Product 1

HCID 178456004HCID 178456004, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 313 mg 1.18 mmol) of t-butoxycarbonyl-L-phenylalanine. 460 mg (1.18 mmol) of (S)-α-amino-N-[(1S,2S,4S)-1-(cyclohexylmethyl)-2-hydroxy-4-isopropyl-5-hexenyl]imidazole-4-propionamide, 0.15 ml (1.18 mmol) of 4-ethylmorpholine, 320 mg (2.36 mmol) of HOBT and 292 mg (1.42 mmol) of DCC in 20 ml of dimethylformamide was stirred at room temperature overnight. Thereafter, the separated precipitate was filtered off and the solvent was evaporated in a high vacuum. The residue was dissolved in ethyl acetate and then washed in succession with 2N sodium bicarbonate solution, saturated ammonium chloride solution, again with 2N sodium bicarbonate solution and again with saturated ammonium chloride solution. After drying the organic solution over sodium sulfate, the solvent was evaporated under reduced pressure and, for purification, the residue (870 mg) was chromatographed on 30 g of silica gel using a 20:1:0.1 mixture of methylene chloride, methanol and ammonia as the eluting agent. Crystallization of the thus-obtained crude product from methylene chloride/ether yielded 410 mg of t-butyl [(S)-α-[[(S)-1-[[(1S,2S,4S)-1-(cyclohexylmethyl)-2-hydroxy-4-isopropyl-5-hexenyl]carbamoyl]-2-imidazol-4-ylethyl]-carbamoyl]phenethyl]carbamate, melting point 161°.

Workup

  1. filtrationThereafter, the separated precipitate was filtered off
  2. customthe solvent was evaporated in a high vacuum
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed in succession with 2N sodium bicarbonate solution, saturated ammonium chloride solution, again with 2N sodium bicarbonate solution and again with saturated ammonium chloride solution
  5. dry with materialAfter drying the organic solution over sodium sulfate
  6. customthe solvent was evaporated under reduced pressure and, for purification
  7. customthe residue (870 mg) was chromatographed on 30 g of silica gel using
  8. additiona 20:1:0.1 mixture of methylene chloride, methanol and ammonia as the eluting agent
  9. customCrystallization of the
  10. customthus-obtained crude product from methylene chloride/ether

Sources & evidence

ORD record
ord-a255048b43f94f9bb81c5c9efc263080
Source dataset
uspto-grants-1993_10
Patent number
US05250517

Reaction notes

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