Oxalyl chloride → HCID 54386688, compound

HRID 2268592Notes

Reaction equation

HRID 2268592 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([O:11][C:12]([N:14]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([Cl:27])[CH:26]=1)[C:21](O)=[O:22])=[O:13])([CH3:10])([CH3:9])[CH3:8].[CH3:34][C:35]1([CH3:52])[O:39][CH:38]([CH2:40][O:41][CH2:42][CH2:43][NH:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[F:51])[CH2:37][O:36]1.CCN(C(C)C)C(C)C>ClCCl.CN(C1C=CN=CC=1)C.CN(C=O)C>[C:7]([O:11][C:12](=[O:13])[N:14]([CH2:15][CH2:16][O:17][C:18]1[CH:19]=[C:20]([C:21](=[O:22])[N:44]([CH2:43][CH2:42][O:41][CH2:40][CH:38]2[CH2:37][O:36][C:35]([CH3:52])([CH3:34])[O:39]2)[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[F:51])[CH:24]=[C:25]([Cl:27])[CH:26]=1)[C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 18348844HCID 18348844, compoundHCID 18348849Benzoic acid,3-chloro-5-[2-[[(1,1-dimethylethoxy)carbonyl]-4-pyridinylamino]ethoxy]-

Product 1

HCID 54386688HCID 54386688, compoundYield 35.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×

Procedure

2M Oxalyl chloride solution in dichloromethane (0.115 ml), and DMF (0.005 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.060 g) in anhydrous dichloromethane (5 ml). The reaction was stirred at room temperature for 1.5 h then [2-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-ethyl]-(2-fluoro-phenyl)-amine (0.121 g) as a solution in dichloromethane (0.5 ml), DMAP (0.005 g) and DIPEA (0.080 ml) were added. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with further dichloromethane and extracted with saturated aqueous sodium bicarbonate. The aqueous layer was removed and the organic phase washed with water and dried with brine and over sodium sulphate and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with ethyl acetate:petroleum ether (1:1, 2:1 and 4:1 v/v) and neat ethyl acetate, to give the title compound as a colourless gum (0.035 g).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 20 h
  2. extractionextracted with saturated aqueous sodium bicarbonate
  3. customThe aqueous layer was removed
  4. washthe organic phase washed with water
  5. dry with materialdried with brine and over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography
  8. washeluting with ethyl acetate:petroleum ether (1:1, 2:1 and 4:1 v/v) and neat ethyl acetate

Sources & evidence

ORD record
ord-4617d57d71cd4b9aad6436b43ca97c2f
Source dataset
uspto-grants-2001_12
Patent number
US06326386B1

Reaction notes

Loading…