Oxalyl chloride → {[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-acetic acid tert-butyl ester

HRID 1040544Notes

Reaction equation

HRID 1040544 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13]3=[N:14][CH:15]=[C:16]([C:17](O)=[O:18])[N:12]3[C@:11]([CH3:32])([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=3)[C:10]2=[O:33])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[C:49]([O:53][C:54](=[O:57])[CH2:55][NH2:56])([CH3:52])([CH3:51])[CH3:50]>C(Cl)Cl.CN(C=O)C>[C:49]([O:53][C:54](=[O:57])[CH2:55][NH:56][C:17]([C:16]1[N:12]2[C@:11]([CH3:32])([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][C:28]([F:29])([F:31])[F:30])=[CH:23][CH:22]=3)[C:10](=[O:33])[N:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:13]2=[N:14][CH:15]=1)=[O:18])([CH3:52])([CH3:51])[CH3:50]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 151417Glycine tert-butyl esterHCID 58431229(R)-7-(3,5-Dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid

Product 1

HCID 58431140{[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-acetic acid tert-butyl esterYield 78.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid (0.500 g, 1.0 mmol) in CH2Cl2 (15 mL) was added oxalyl chloride (0.194 mL, 2.2 mmol), followed by slow addition of DMF (0.05 mL). The reaction was stirred for 90 min. The volatiles were removed in vacuo, and the residue dissolved in THF (15 mL). To this cloudy solution was added diisopropylethylamine (0.88 mL, 5.0 mmol) followed by glycine tert-butyl ester (0.30 mL, 2.2 mmol). The reaction was stirred for another 14 h. The volatiles were removed in vacuo at 40° C. The reaction mixture was diluted with ethyl acetate and washed with 1 N aqueous HCl (×2), 10% aqueous Na2CO3 (×2) and brine (×2). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo to afford {[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-acetic acid tert-butyl ester (0.483 g) as a colorless foam.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue dissolved in THF (15 mL)
  3. stirringThe reaction was stirred for another 14 h
  4. customThe volatiles were removed in vacuo at 40° C
  5. additionThe reaction mixture was diluted with ethyl acetate
  6. washwashed with 1 N aqueous HCl (×2), 10% aqueous Na2CO3 (×2) and brine (×2)
  7. dry with materialThe organic phase was dried over anhydrous Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-269e67a92bff4fc0995aabfcb1f2380c
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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