Diisopropylethylamine → (S)-benzyl 3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoate

HRID 333304Notes

Reaction equation

HRID 333304 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1([C:11]([OH:13])=O)[CH2:10][CH2:9][CH2:8][CH2:7]1)[CH3:2].Cl.[NH2:16][C@@H:17]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:31][CH:30]=1)[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].CCN=C=NCCCN(C)C.Cl.ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:32]1([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:33]=[CH:34][C:29]([CH2:28][C@H:17]([NH:16][C:11]([C:6]2([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:14])[CH2:7][CH2:8][CH2:9][CH2:10]2)=[O:13])[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[CH:30][CH:31]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68753467HCID 68753467, compoundHCID 68805074(S)-benzyl 2-amino-3-(biphenyl-4-yl)propanoate hydrochloride

Product 1

HCID 70122800(S)-benzyl 3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoateYield 85.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxylic acid (672 mg, 3.36 mmol), (S)-benzyl 2-amino-3-(biphenyl-4-yl)propanoate hydrochloride (957 mg, 2.60 mmol), WSC.HCl (833 mg, 4.34 mmol), 1-hydroxy-7-azabenzotriazole (591 mg, 4.34 mmol) and DIPEA (0.759 ml, 4.34 mmol) in DMF (15 ml) was allowed to stir at room temperature for 2 hours. The reaction was quenched with H2O (10 ml) and 35% NH4OH aqueous (2 ml). The mixture was stirred for 30 minutes. The product was extracted with EtOAc, washed twice with 1 M HCl aqueous, once with H2O, and then once with brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 60:40) to give (S)-benzyl 3-(biphenyl-4-yl)-2-(1-(2-ethoxy-2-oxoethyl)cyclopentanecarboxamido)propanoate (1.143 g).

Workup

  1. customThe reaction was quenched with H2O (10 ml) and 35% NH4OH aqueous (2 ml)
  2. stirringThe mixture was stirred for 30 minutes
  3. extractionThe product was extracted with EtOAc
  4. washwashed twice with 1 M HCl aqueous, once with H2O
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 60:40)

Sources & evidence

ORD record
ord-a1e4164d2b4c477e8b62d2a30905013a
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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