Triethylamine → (S)-1-[2-t-Butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidine

HRID 1419592Notes

Reaction equation

HRID 1419592 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].[O:31]=[C:32]1[N:36]([CH:37]2[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]2)[C:35]2[CH:43]=[CH:44][CH:45]=[CH:46][C:34]=2[NH:33]1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(=O)([O-])O.[Na+]>ClCCl.O>[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:17]([N:40]1[CH2:39][CH2:38][CH:37]([N:36]2[C:35]3[CH:43]=[CH:44][CH:45]=[CH:46][C:34]=3[NH:33][C:32]2=[O:31])[CH2:42][CH2:41]1)=[O:19])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 886381,3-Dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-oneHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 516892Sodium BicarbonateHCID 11760269(S)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionic acid

Product 1

HCID 11146146(S)-1-[2-t-Butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidineYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.28 mL, 0.20 g, 2 mmol) was added to a stirred, cooled (0° C.) mixture of (S)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionic acid (prepared according to the method of Sugano. H, and Miyoshi. M, J. Org. Chem 1976, 41, 2352) (364 mg, 1 mmol), 4-(2-keto-1-benzimidazolinyl)piperidine (217 mg, 1 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (305 mg, 2 mmol) in dichloromethane (10 mL) and the mixture was stirred at room temperature for 1h. Aqueous sodium hydrogen carbonate (saturated, 40 mL) and water (10 mL) were added and the mixture was extracted with dichloromethane (3×50 mL). The combined organic fractions were washed with aqueous citric acid (10%, 2×50 mL), aqueous sodium hydrogen carbonate (saturated, 2×50 mL) and brine (50 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH (99:1) to give the title compound as a colorless foam (318 mg, 56%). m/e (ES+) 563 (MH+).

Workup

  1. temperaturecooled
  2. customprepared
  3. extractionthe mixture was extracted with dichloromethane (3×50 mL)
  4. washThe combined organic fractions were washed with aqueous citric acid (10%, 2×50 mL), aqueous sodium hydrogen carbonate (saturated, 2×50 mL) and brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with CH2Cl2 /MeOH (99:1)

Sources & evidence

ORD record
ord-95f4338a314e4ae59dbfd207cc259666
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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