Acetonitrile → (S)-2-[(5-chloro-2-formyl-2H-chromen-3-ylmethyl)-methyl-amino]-4-methyl-pentanoic acid methyl ester

HRID 1925884Notes

Reaction equation

HRID 1925884 reaction equation
C[O:2][C:3]([CH:5]1[C:14]([CH2:15][NH:16][C@H:17]([C:22]([O:24][CH3:25])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[Cl:26])[O:6]1)=O.[C:27](#N)C>>[CH3:25][O:24][C:22](=[O:23])[C@@H:17]([N:16]([CH2:15][C:14]1[CH:5]([CH:3]=[O:2])[O:6][C:7]2[C:12]([CH:13]=1)=[C:11]([Cl:26])[CH:10]=[CH:9][CH:8]=2)[CH3:27])[CH2:18][CH:19]([CH3:20])[CH3:21]

Participants

3

Reactant 2

HCID 6342AcetonitrileHCID 675219645-chloro-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid methyl ester

Product 1

HCID 86660535(S)-2-[(5-chloro-2-formyl-2H-chromen-3-ylmethyl)-methyl-amino]-4-methyl-pentanoic acid methyl esterYield 71.4%

Procedure

A solution of 5-chloro-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid methyl ester (1.4 g, 3.53 mmol) and N,N′-diisopropylethyl amine (2.44 mL, 14.14 mmol) in acetonitrile (3 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 using flash chromatography over neutral alumina (eluant-hexanes-ethyl acetate 1:3, Rf=0.3) to afford (S)-2-[(5-chloro-2-formyl-2H-chromen-3-ylmethyl)-methyl-amino]-4-methyl-pentanoic acid methyl ester (1.02 g, 71.4%) as a 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

Sources & evidence

ORD record
ord-5825881b95654710b1278b1699098abf
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

Loading…