5-chloro-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester → (S)-2-(8-chloro-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid methyl ester

HRID 1925916Notes

Reaction equation

HRID 1925916 reaction equation
C([O:3][C:4]([CH:6]1[C:15]([CH2:16][NH:17][C@H:18]([C:26]([O:28][CH3:29])=[O:27])[CH2:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[Cl:30])[O:7]1)=O)C>C(#N)C>[CH3:29][O:28][C:26](=[O:27])[C@@H:18]([N:17]1[CH2:16][C:15]2=[CH:14][C:13]3[C:12]([Cl:30])=[CH:11][CH:10]=[CH:9][C:8]=3[O:7][CH:6]2[C:4]1=[O:3])[CH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

3

Reactant 1

HCID 675214015-chloro-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester

Product 1

HCID 67520933(S)-2-(8-chloro-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid methyl esterYield 48.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 5-chloro-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (0.55 g, 1.26 mmol) and N,N′-diisopropylethyl amine (0.87 mL, 5.05 mmol) in acetonitrile (2 mL) was heated in a sealed tube at 140° C. for 48 hours. The reaction mixture, after aqueous work-up, was extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated in vacuo and the residue was purified over neutral alumina using hexanes-ethyl acetate (1:1.2) as eluents to afford (S)-2-(8-chloro-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-3-cyclohexyl-propionic acid methyl ester (0.24 g, 48.8%) as a off white solid.

Workup

  1. extractionThe reaction mixture, after aqueous work-up, was extracted with ethyl acetate (3×)
  2. washThe combined ethyl acetate layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was purified over neutral alumina

Sources & evidence

ORD record
ord-905e880bb00c44098371f3f5aa814fe2
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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