Water → HCID 68958663, compound

HRID 1888368Notes

Reaction equation

HRID 1888368 reaction equation
S(Cl)(Cl)=O.[Br:5][CH2:6][C@@:7]([OH:12])([CH3:11])[C:8](O)=[O:9].[CH3:13][O:14][C:15](=[O:25])[C:16]1[CH:21]=[C:20]([NH2:22])[CH:19]=[CH:18][C:17]=1[C:23]#[N:24].O>C1COCC1.CN(C)C(=O)C>[CH3:13][O:14][C:15](=[O:25])[C:16]1[CH:21]=[C:20]([NH:22][C:8](=[O:9])[C@:7]([OH:12])([CH3:11])[CH2:6][Br:5])[CH:19]=[CH:18][C:17]=1[C:23]#[N:24]

Participants

7

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 10582468(2R)-3-bromo-2-hydroxy-2-methylpropanoic acidHCID 53419719Methyl 5-amino-2-cyanobenzoate

Product 1

HCID 68958663HCID 68958663, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

Thionyl chloride (3.9 ml, 5.3 mmol) was added dropwise to a solution of (2R)-3-bromo-2-hydroxy-2-methylpropionic acid (8.19 g, 44.8 mmol, prepared as described in WO 2005/000794) in 190 ml of THF and 5.8 ml of N,N-dimethyl-acetamide (DMAC) at 5° C. under nitrogen atmosphere. The solution was stirred for 3 h at room temperature. A solution of 5-amino-2-cyanobenzoic acid methyl ester (7.50 g, 4.3 mmol) in 75 ml of THF was added and the reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h. The mixture was poured into water, extracted with ethyl acetate, washed with water, dried over Na2SO4 and evaporated under reduced pressure. The crude product was stirred in toluene and filtration afforded the purified compound.

Workup

  1. temperaturethe reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h
  2. extractionextracted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated under reduced pressure
  6. stirringThe crude product was stirred in toluene
  7. filtrationfiltration
  8. customafforded the purified compound

Sources & evidence

ORD record
ord-87c0fc08456443678e10e64ebfe66799
Source dataset
uspto-grants-2013_08
Patent number
US08501814B2

Reaction notes

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