2,2-Dimethyl-3-acetyloxypropionyl chloride → (3S)-1-Cbz-3-[cyclohexyl(acetyloxypivaloyl)amino]pyrrolidine

HRID 1670008Notes

Reaction equation

[C:1]([N:11]1[CH2:15][CH2:14][C@H:13]([NH:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH3:23][C:24]([CH3:33])([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C:25](Cl)=[O:26]>CN(C1C=CN=CC=1)C.C1COCC1>[C:1]([N:11]1[CH2:15][CH2:14][C@H:13]([N:16]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:25](=[O:26])[C:24]([CH3:33])([CH3:23])[CH2:28][O:29][C:30](=[O:32])[CH3:31])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To the mixture of (3S)-1-Cbz-3-(cyclohexylamino)pyrrolidine (3.0 g, 10 mmol), TEA (15 mL), and DMAP (1.25 g, 10 mmol) in THF (15 mL) was added 2,2-dimethyl-3-acetyloxypropionyl chloride (3.58 g, 20 mmol) prepared in Step A. After the reaction mixture was refluxed for 48 h (90-110° C.), the solvent was removed, and the residue was diluted with an aqueous NaHCO3 solution was added to the residue. The organic material was extracted with EtOAc, and the extracts were washed by 1N HCl, dried over MgSO4, and concentrated in vacuo. The crude product was purified by column chomatography (EtOAc/Hex=1/2) to give the title compound (2.80 g, 62.9%).

Workup

customthe solvent was removed
additionthe residue was diluted with an aqueous NaHCO3 solution
additionwas added to the residue
extractionThe organic material was extracted with EtOAc
washthe extracts were washed by 1N HCl
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe crude product was purified by column chomatography (EtOAc/Hex=1/2)

Sources & evidence

ORD record: ord-f6215a36d3434bccbb8d9d08471945b0
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989634B2

Reaction notes

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