1,2-Dichloroethane → cyclopentyl (2S)-[(tert-butoxycarbonyl)amino](cyclohexyl)acetate

HRID 475046Notes

Reaction equation

HRID 475046 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9](CC1CCCCC1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:20]1([OH:25])[CH2:24][CH2:23][CH2:22][CH2:21]1.[CH2:26](Cl)[CH2:27]Cl>CN(C=O)C.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:27]1[CH2:26][CH2:22][CH2:21][CH2:20][CH2:24]1)[C:10]([O:25][CH:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 7298CyclopentanolHCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Product 1

HCID 57658394cyclopentyl (2S)-[(tert-butoxycarbonyl)amino](cyclohexyl)acetateYield 235.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-tert-butoxycarbonylamino-3-cyclohexyl-propionic acid (5 g, 19.4 mmol) in DMF (50 mL) at 0° C. was added cyclopentanol (8.8 ml, 97.15 mmol), EDC (4.09 g, 21.37 mmol) and finally DMAP (237 mg, 1.94 mmol). The reaction mixture was warmed to RT and stirred for 18 h. The DMF was removed in vacuo to give a clear oil. This was separated between water and EtOAc. The organic phase was dried (MgSO4) and concentrated in vacuo. The crude extract was purified by column chromatography (25% EtOAC in heptane) to yield the desired product as a clear oil (14.87 g, 55%). 1H NMR (300 MHz, d6-DMSO) δ: 7.09 (1H, d), 5.08 (1H, t), 3.76 (1H, t), 1.50-1.85 (10H, br m), 1.39 (9H, s), 1.00-1.25 (9H, br m).

Workup

  1. customThe DMF was removed in vacuo
  2. customto give a clear oil
  3. customThis was separated between water and EtOAc
  4. dry with materialThe organic phase was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. extractionThe crude extract
  7. customwas purified by column chromatography (25% EtOAC in heptane)

Sources & evidence

ORD record
ord-516d9d60025d492aa40512b535ee8875
Source dataset
uspto-grants-2014_01
Patent number
US08637547B2

Reaction notes

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