Dichloromethane → HCID 13022580, compound

HRID 443467Notes

Reaction equation

HRID 443467 reaction equation
C(Cl)Cl.[Cl:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[NH:15][C@H:16]([CH:20]([CH3:22])[CH3:21])[C:17]([OH:19])=[O:18].[C:23]([C@@H:25](O)[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:27]=1)#[N:24].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[Cl:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[NH:15][C@H:16]([CH:20]([CH3:22])[CH3:21])[C:17]([O:19][C@H:25]([C:23]#[N:24])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:27]=1)=[O:18]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10868DicyclohexylcarbodiimideHCID 2316094(R)-2-((2-Chloro-4-(trifluoromethyl)phenyl)amino)-3-methylbutanoic acidHCID 9837437(2S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile

Product 1

HCID 13022580HCID 13022580, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Procedure

Into 4.5 ml of methylene chloride containing 22.5 mg of 4-dimethylaminopyridine are added 439 mg (1.48 mmol) of (R)-2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoic acid and 329 mg (1.46 mmol) of (S)-α-cyano-3-phenoxybenzyl alcohol. The solution is cooled in an ice bath and 380 mg (1.82 mmol) of dicyclohexylcarbodiimide is added. The mixture is stirred at 0° for 1 hour and is then worked up by partition between ether/hexane. The aqueous phase is extracted with ether, and the ether extract is washed with water (2×) and brine, dried over magnesium sulfate, filtered and evaporated. The product is purified by radial thin layer chromatography (2 mm silica gel rotor eluting with 12% ether/hexane). Higher diastereomeric purity is obtained by further radial tlc, yielding the final product (S)-α-cyano-3-phenoxybenzyl (R)-2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoate, specific rotation=+46.3° (in CHCl3), diastereomer purity=~98%.

Workup

  1. temperatureThe solution is cooled in an ice bath
  2. customby partition between ether/hexane
  3. extractionThe aqueous phase is extracted with ether
  4. extractionthe ether extract
  5. washis washed with water (2×) and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe product is purified by radial thin layer chromatography (2 mm silica gel rotor eluting with 12% ether/hexane)
  10. customHigher diastereomeric purity is obtained by further radial tlc

Sources & evidence

ORD record
ord-27acffbb472c480a83db8197031ab156
Source dataset
uspto-grants-1981_04
Patent number
US04260633

Reaction notes

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