Chloroacetyl chloride → HCID 57889186, compound

HRID 1820192Notes

Reaction equation

HRID 1820192 reaction equation
Cl.[NH2:2][C@H:3]([CH:19]([CH3:21])[CH3:20])[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[Cl:22][CH2:23][C:24](Cl)=[O:25]>C(Cl)Cl>[Cl:22][CH2:23][C:24]([NH:2][C@H:3]([CH:19]([CH3:21])[CH3:20])[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:8][CH2:7]1)=[O:5])=[O:25]

Participants

4

Reactant 2

HCID 6577Chloroacetyl chloride2×HCID 67299489HCID 67299489, compound

Product 1

HCID 57889186HCID 57889186, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-2-amino-1-(4-(4-chlorophenyl)piperidin-1-yl)-3-methylbutan-1-one hydrochloride (340 mg, 1.03 mmol) in DCM (10 mL) cooled to 0° C. was added TEA (144 μL, 1.03 mmol) followed by chloroacetylchloride (82 μL, 1.03 mmol). Upon completion of addition, the reaction mixture was held at 0° C. for 4 h. After this time, an additional aliquot of chloroacetyl chloride (60 μL) was added followed by additional TEA (150 μL). The resulting solution was diluted with dichloromethane (40 mL) and quenched by the addition of aqueous NaHCO3 (25 mL). The layers were separated. The organic layer was dried over Na2SO4, filtered, and concentrated to yield a residue. The residue was purified via SiO2 chromatography (20% to 50% EtOac/heptane) to give (R)-2-chloro-N-(1-(4-(4-chlorophenyl)piperidin-1-yl)-3-methyl-1-oxobutan-2-yl)acetamide as a clear glassy solid (349 mg, 92% yield). MS found: 371.3 (M+), 373.3 (M+2).

Workup

  1. additionUpon completion of addition
  2. customquenched by the addition of aqueous NaHCO3 (25 mL)
  3. customThe layers were separated
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue
  8. customThe residue was purified via SiO2 chromatography (20% to 50% EtOac/heptane)

Sources & evidence

ORD record
ord-8e3102c88d0f464dba8e881b6c9d9c79
Source dataset
uspto-grants-2009_10
Patent number
US07601844B2

Reaction notes

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