Oxalyl chloride → HCID 54300940, compound

HRID 2268588Notes

Reaction equation

HRID 2268588 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][O:35][C:36](=[O:48])[CH2:37][CH2:38][CH2:39][NH:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[F:47].CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:34][O:35][C:36](=[O:48])[CH2:37][CH2:38][CH2:39][N:40]([C:21](=[O:22])[C:20]1[CH:24]=[C:25]([Cl:27])[CH:26]=[C:18]([O:17][CH2:16][CH2:15][N:14]([C:12]([O:11][C:7]([CH3:9])([CH3:8])[CH3:10])=[O:13])[C:28]2[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=2)[CH:19]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[F:47]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 18348849Benzoic acid,3-chloro-5-[2-[[(1,1-dimethylethoxy)carbonyl]-4-pyridinylamino]ethoxy]-HCID 43377911Methyl 4-[(2-fluorophenyl)amino]butanoate

Product 1

HCID 54300940HCID 54300940, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

2M Oxalyl chloride solution in dichloromethane (0.600 ml) and DMF (0.01 ml) were added to a suspension of 3-[2-(tert-butoxycarbonyl-pyridin-4-yl-amino)-ethoxy]-5-chloro-benzoic acid (0.393 g) in anhydrous dichloromethane (5 ml). The reaction was stirred at room temperature for 1 h then a solution of 4-(2-fluoro-phenylamino)-butyric acid methyl ester (0.422 g) in dichloromethane (1.5 ml), DMAP (0.006 g) and DIPEA (0.522 ml) were added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous layer was removed and the organic phase washed with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, 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:cyclohexane (4:1 v/v), to give the title compound as a colourless gum (0.287 g).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. customThe aqueous layer was removed
  4. washthe organic phase washed with 1M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, 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:cyclohexane (4:1 v/v)

Sources & evidence

ORD record
ord-04131c74e0aa45eaba65f7359dd4ba32
Source dataset
uspto-grants-2001_12
Patent number
US06326386B1

Reaction notes

Loading…