Chloroacetyl chloride → HCID 86668084, compound

HRID 474115Notes

Reaction equation

HRID 474115 reaction equation
[NH2:1][C@@:2]([C:8]1[C:13]([F:14])=[C:12]([Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])[CH:11]=[C:10]([Br:22])[N:9]=1)([CH:5]([F:7])[F:6])[CH2:3][OH:4].C(=O)([O-])[O-].[Na+].[Na+].[Cl:29][CH2:30][C:31](Cl)=[O:32]>ClCCl>[Br:22][C:10]1[N:9]=[C:8]([C@@:2]([NH:1][C:31](=[O:32])[CH2:30][Cl:29])([CH2:3][OH:4])[CH:5]([F:6])[F:7])[C:13]([F:14])=[C:12]([Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])[CH:11]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 10340Sodium CarbonateHCID 86668085HCID 86668085, compound

Product 1

HCID 86668084HCID 86668084, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-amino-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-3,3-difluoro-propan-1-ol (2.15 g, 5.38 mmol) in dichloromethane (14.55 ml) was added an aq. sodium carbonate solution (14.55 ml, 10% aq. solution) at 0° C. 2-Chloroacetyl chloride (0.518 ml, 6.46 mmol) was added dropwise at 0° C. and the ice bath was removed after the addition. The reaction mixture was stirred at rt for 15 min. Methanol was added and the reaction mixture was stirred at 50° C. for 10 min. The reaction mixture was diluted with dichloromethane and water. The mixture was extracted with dichloromethane, dried over sodium sulfate, filtered and evaporated. The crude light yellow oil (2.91 g) was chromatographed over silica gel (40 g redisep column, cyclohexane/ethyl acetate 10-70%) to give the title compound. 2.32 g (91% yield).

Workup

  1. customthe ice bath was removed
  2. additionafter the addition
  3. additionMethanol was added
  4. stirringthe reaction mixture was stirred at 50° C. for 10 min
  5. additionThe reaction mixture was diluted with dichloromethane and water
  6. extractionThe mixture was extracted with dichloromethane
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude light yellow oil (2.91 g) was chromatographed over silica gel (40 g redisep column, cyclohexane/ethyl acetate 10-70%)

Sources & evidence

ORD record
ord-994612a5d81947e6a7259eadcdd6d88c
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

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