1,2-Dichloroethane → methyl (S)-alpha-[(S)-alpha-[(t-butylsulphonyl)methyl]hydrocinnamamido]imidazolepropionate

HRID 2294692Notes

Reaction equation

HRID 2294692 reaction equation
[C:1]([S:5]([CH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([OH:12])=O)(=[O:7])=[O:6])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:22][O:23][C:24](=[O:33])[C@H:25]([CH2:27][C:28]1[N:32]=CNC=1)[NH2:26].C([N:36]1CCOCC1)C.C1C=CC2N(O)N=NC=2C=1.[CH2:52](Cl)[CH2:53]Cl>CN(C)C=O>[C:1]([S:5]([CH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([NH:26][C@@H:25]([CH2:27][C:28]1[NH:32][CH:52]=[CH:53][N:36]=1)[C:24]([O:23][CH3:22])=[O:33])=[O:12])(=[O:6])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 9860623(S)-alpha-[(t-butylsulphonyl)methyl]hydrocinnamic acidHCID 178419105HCID 178419105, compound

Product 1

HCID 67931045methyl (S)-alpha-[(S)-alpha-[(t-butylsulphonyl)methyl]hydrocinnamamido]imidazolepropionate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5.7 (20 mmol) of (S)-α-[(tert-butylsulphonyl)methyl)hydrocinnamic acid (EPA 0236734) 4.85 g (20 mmol) of L-histidine methyl ester dihydrochloride, 10.3 ml (81.7 mmol) of N-ethylmorpholine and 2.98 g (20 mmol) of HOBT in 85 ml of dimethylformamide is treated portionwise at 0°-2° under argon with 4.23 g (22 mmol) of EDC and subsequently stirred at room temperature overnight. Thereafter, the solvent is evaporated in a high vacuum, the residue is taken up in 100 ml of ethyl acetate and washed in sequence three times with 10 ml of 2N sodium bicarbonate solution, twice with 10 ml of saturated sodium chloride solution, twice with 10 ml of saturated ammonium chloride solution and twice with 5 ml of saturated sodium chloride solution. The aqueous phases are extracted three times with 20 ml of ethyl acetate and the pooled organic phases are dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product obtained (9.4 g) is chromatographed on 300 g of silica gel using a 95:5 mixture of methylene chloride and methanol as the eluent. There are obtained 8.6 g of methyl (S)-α-[(S)-α-[(tert-butylsulphonyl)methyl]hydrocinnamamido]imidazolpropionate as a colourless foam; MS: 436 (M+H)+.

Workup

  1. customThereafter, the solvent is evaporated in a high vacuum
  2. washwashed in sequence three times with 10 ml of 2N sodium bicarbonate solution, twice with 10 ml of saturated sodium chloride solution, twice with 10 ml of saturated ammonium chloride solution and twice with 5 ml of saturated sodium chloride solution
  3. extractionThe aqueous phases are extracted three times with 20 ml of ethyl acetate
  4. dry with materialthe pooled organic phases are dried over sodium sulphate
  5. customevaporated under reduced pressure
  6. customFor purification
  7. customthe crude product obtained (9.4 g)
  8. customis chromatographed on 300 g of silica gel using
  9. additiona 95:5 mixture of methylene chloride and methanol as the eluent

Sources & evidence

ORD record
ord-b667b6524fb24e6abc6ecdd879cbb062
Source dataset
uspto-grants-1997_11
Patent number
US05688946

Reaction notes

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