Oxalyl chloride → HCID 58288339, compound

HRID 1476087Notes

Reaction equation

HRID 1476087 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]([C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])[C:15]([OH:17])=O)=[CH:10][CH:9]=1.C(N(CC)C(C)C)(C)C.[NH2:33][C:34]1[CH:35]=[C:36]([CH2:42][CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:37]=[CH:38][C:39]=1[C:40]#[N:41]>ClCCl.CN(C=O)C.C1COCC1.O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C@H:14]([C@@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])[C:15]([NH:33][C:34]2[CH:35]=[C:36]([CH2:42][CH2:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:37]=[CH:38][C:39]=2[C:40]#[N:41])=[O:17])=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 58288396(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acidHCID 58288428HCID 58288428, compound

Product 1

HCID 58288339HCID 58288339, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., 155 μl (0.31 mmol) of a 2 M solution of oxalyl chloride in dichloromethane and one drop of DMF were added to a solution of 41.3 mg (0.16 mmol) of (2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid in 1.16 ml of dichloromethane. After 1 h of stirring at 0° C., the mixture was concentrated, the residue that remained was dissolved in 1 ml of THF, 32 μl (0.19 mmol) of N,N-diisopropylethylamine were added, the mixture was cooled to 0° C. and a solution of 42 mg (0.17 mmol) of tert-butyl 3-(3-amino-4-cyanophenyl)propanoate in 2 ml of THF was added. The reaction mixture was stirred at RT overnight. The mixture was then poured into 10 ml of water and extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated. The residue was purified by preparative HPLC. This gave 16.5 mg (22% of theory) of the title compound.

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutionthe residue that remained was dissolved in 1 ml of THF
  3. temperaturethe mixture was cooled to 0° C.
  4. stirringThe reaction mixture was stirred at RT overnight
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic phases were dried over magnesium sulphate
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ddf8b7c2aabb4353a0853c0d6212b641
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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