5-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester → (S)-2-(8-methoxy-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid methyl ester

HRID 1925899Notes

Reaction equation

HRID 1925899 reaction equation
C([O:3][C:4]([CH:6]1[C:15]([CH2:16][NH:17][C@H:18]([C:23]([O:25][CH3:26])=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:27][CH3:28])[O:7]1)=O)C>C(#N)C>[CH3:26][O:25][C:23](=[O:24])[C@@H:18]([N:17]1[CH2:16][C:15]2=[CH:14][C:13]3[C:12]([O:27][CH3:28])=[CH:11][CH:10]=[CH:9][C:8]=3[O:7][CH:6]2[C:4]1=[O:3])[CH2:19][CH:20]([CH3:21])[CH3:22]

Participants

3

Reactant 1

HCID 675204455-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester

Product 1

HCID 67521765(S)-2-(8-methoxy-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid methyl esterYield 63.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 5-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (0.45 g, 1.14 mmol) and N,N′-diisopropylethyl amine (0.8 mL, 4.50 mmol) in acetonitrile (2 mL) was heated in a sealed tube at 140° C. for 48 hours. The reaction mixture, after aqueous work-up, 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 as eluents to afford (S)-2-(8-methoxy-3-oxo-3,3a-dihydro-1H-chromeno[2,3-c]pyrrol-2-yl)-4-methyl-pentanoic acid methyl ester (0.25 g, 62.9%) as a solid.

Workup

  1. extractionThe reaction mixture, after aqueous work-up, 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-c38b0f790b694d11a5b6a7eb97bad4e6
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

Loading…