Diisopropylethylamine → N-4-cyanobenzoyl-beta-phenyl-alpha,alpha-dimethyl-beta-alanyl-4-piperidineacetic acid benzyl ester

HRID 361748

Reaction equation

HRID 361748 reaction equation
[C:1]([C:3]1[CH:24]=[CH:23][C:6]([C:7]([NH:9][CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]([CH3:16])([CH3:15])[C:12](O)=[O:13])=[O:8])=[CH:5][CH:4]=1)#[N:2].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH2:61]([O:68][C:69](=[O:77])[CH2:70][CH:71]1[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1)[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C(Cl)Cl>[CH2:61]([O:68][C:69](=[O:77])[CH2:70][CH:71]1[CH2:72][CH2:73][N:74]([C:12](=[O:13])[C:11]([CH3:15])([CH3:16])[CH:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:9][C:7](=[O:8])[C:6]2[CH:23]=[CH:24][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH2:75][CH2:76]1)[C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 15380360Phenylmethyl 4-piperidineacetateHCID 70199446N-4-cyanobenzoyl-beta-phenyl-alpha,alpha-dimethyl-beta-alanine

Product 1

HCID 86753668N-4-cyanobenzoyl-beta-phenyl-alpha,alpha-dimethyl-beta-alanyl-4-piperidineacetic acid benzyl esterYield 69.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-4-Cyanobenzoyl-β-phenyl-α,α-dimethyl-β-alanine (0.5 g, 1.55 mmol) was dissolved in methylene chloride (30 ml). To the resulting solution, BOP reagent (0.89 g, 4.03 mmol) and diisopropylethyl-amine (DIEA) (1.67 ml, 9.3 mmol) were added under cooling with ice and the mixture was stirred for 30 minutes. To the reaction mixture was added 4-piperidineacetic acid benzyl ester (1.08 g, 4.65 mmol) and the resulting mixture was stirred overnight. After the solvent was distilled off, the residue was dissolved in ethyl acetate, washed sequentially with a 5% aqueous solution of citric acid, a 5% aqueous solution of sodium bicarbonate and a saturated aqueous solution of NaCl 3 times each and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was applied to a silica gel column (2.2×20 cm) and eluted with a mixed solution (hexane:ethyl acetate=3:1). The desired fractions were collected and the solvents were distilled off to yield an oil of N-4-cyanobenzoyl-β-phenyl-α,α-dimethyl-β-alanyl-4-piperidineacetic acid benzyl ester (0.58 g, 69.6%).

Workup

  1. temperatureunder cooling with ice
  2. stirringthe resulting mixture was stirred overnight
  3. distillationAfter the solvent was distilled off
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed sequentially with a 5% aqueous solution of citric acid
  6. dry with materiala 5% aqueous solution of sodium bicarbonate and a saturated aqueous solution of NaCl 3 times each and dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off
  8. washeluted with a mixed solution (hexane:ethyl acetate=3:1)
  9. customThe desired fractions were collected
  10. distillationthe solvents were distilled off

Sources & evidence

ORD record
ord-af90b3b59710401e8cfb72c967fa6e7e
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Linked notes

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