1-Phenylcyclopentanecarboxylic acid → (s)-1-Phenyl-cyclopentanecarboxylic acid [2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-amide

HRID 430804

Reaction equation

HRID 430804 reaction equation
[C:1]1([C:7]2([C:12]([OH:14])=O)[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:48][C@@H:49]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([O:64][CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)=[CH:60][CH:59]=1)[C:50]([NH:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51]>CN(C=O)C.C(OCC)C>[CH2:65]([O:64][C:61]1[CH:62]=[CH:63][C:58]([CH2:57][C@H:49]([NH:48][C:12]([C:7]2([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:8][CH2:9][CH2:10][CH2:11]2)=[O:14])[C:50](=[O:51])[NH:52][C:53]([CH3:54])([CH3:55])[CH3:56])=[CH:59][CH:60]=1)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

7

Reactant 4

HCID 661671-Phenylcyclopentanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15517727(S)-2-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide

Product 1

HCID 9892124(s)-1-Phenyl-cyclopentanecarboxylic acid [2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-amideYield 45%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-Phenyl-1-cyclopentanecarboxylic acid (0.171 g, 0.899 mmol) was dissolved in dry DMF (3 mL) under a nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added in succession N,N-diisopropylethylamine (0.310 mL, 1.80 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.341 g, 0.899 mmol, Novabiochem, La Jolla, Calif.). The resulting reaction mixture was stirred at 0° C. for 30 minutes, (S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide (0.293 g, 0.899 mmol) was then added. After an additional 60 minutes stirring at 0° C., the reaction mixture was mixed with 60 mL of diethyl ether. The resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution and brine, and was dried over Na2SO4. The solution was concentrated in vacuo, and an oil was obtained. The crude residue was purified by chromatography (silica gel, 60% ether in hexanes) to give the title compound as a white foam (0.20 g, 45%); mp 40-50° C.

Workup

  1. customThe resulting reaction mixture
  2. stirringAfter an additional 60 minutes stirring at 0° C.
  3. washThe resulting mixture was successively washed with 5% aqueous HCl solution, brine, saturated aqueous NaHCO3 solution and brine
  4. dry with materialwas dried over Na2SO4
  5. concentrationThe solution was concentrated in vacuo
  6. customan oil was obtained
  7. customThe crude residue was purified by chromatography (silica gel, 60% ether in hexanes)

Sources & evidence

ORD record
ord-13f94147e9424f0caa6371d873033357
Source dataset
uspto-grants-2001_11
Patent number
US06323243B1

Linked notes

Loading…