Triethylamine → 5(S)-Tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(3-carbamoylpropyl)]-amide

HRID 725631Notes

Reaction equation

HRID 725631 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][CH2:11][CH2:12][C:13]([NH2:15])=[O:14].C(OP(C#N)(=O)OCC)C.[C:26]([O:30][C:31]([NH:33][C@@H:34]([CH2:50][C@@H:51]([CH:67]([CH3:69])[CH3:68])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=1)[C@@H:35]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[CH2:36][C@@H:37]([CH3:41])[C:38](O)=[O:39])=[O:32])([CH3:29])([CH3:28])[CH3:27]>CN(C)C=O>[C:13]([CH2:12][CH2:11][CH2:10][NH:9][C:38](=[O:39])[C@H:37]([CH3:41])[CH2:36][C@H:35]([O:42][Si:43]([C:46]([CH3:47])([CH3:49])[CH3:48])([CH3:45])[CH3:44])[C@@H:34]([NH:33][C:31]([O:30][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:32])[CH2:50][C@@H:51]([CH:67]([CH3:68])[CH3:69])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[C:55]([O:61][CH2:62][CH2:63][CH2:64][O:65][CH3:66])[CH:54]=1)(=[O:14])[NH2:15]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 30147094-Aminobutyramide monohydrochlorideHCID 228658215(S)-tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid

Product 1

HCID 542315885(S)-Tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(3-carbamoylpropyl)]-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

67 μl of triethylamine, 34 mg of 4-aminobutyric acid amide hydrochloride and 38 μl of cyanophosphonic acid diethyl ester are added in succession to 128 mg of 5(S)-tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid in 8 ml of dimethylformamide at 0° C. The reaction mixture is stirred for a further 18 hours at room temperature. The reaction mixture is concentrated by evaporation and 20 ml of 10% citric acid solution and ice are added to the residue. The mixture is extracted repeatedly with ethyl acetate and the organic phases are then washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution. After concentration by evaporation, the residue is purified by means of FC (70 g of silica gel, dichloromethane/methanol=9:1). The title compound is obtained: Rf (dichloromethane/methanol=9:1)=0.38.

Workup

  1. concentrationThe reaction mixture is concentrated by evaporation and 20 ml of 10% citric acid solution and ice
  2. additionare added to the residue
  3. extractionThe mixture is extracted repeatedly with ethyl acetate
  4. washthe organic phases are then washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
  5. concentrationAfter concentration
  6. customby evaporation
  7. customthe residue is purified by means of FC (70 g of silica gel, dichloromethane/methanol=9:1)

Sources & evidence

ORD record
ord-3e0e757c6d9c46e6ae10b88b75a3f236
Source dataset
uspto-grants-1998_01
Patent number
US05705658

Reaction notes

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