Chloroacetyl chloride → 2-chloro-N-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-acetamide

HRID 643260Notes

Reaction equation

HRID 643260 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:16][C:15]3([CH3:18])[CH2:17][CH:11]2[CH2:12][C:13]([CH3:20])([CH3:19])[CH2:14]3)=[O:9])=[CH:4][CH:3]=1.[Cl:21][CH2:22][C:23](Cl)=[O:24]>C1COCC1>[Cl:21][CH2:22][C:23]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:16][C:15]3([CH3:18])[CH2:17][CH:11]2[CH2:12][C:13]([CH3:20])([CH3:19])[CH2:14]3)=[O:9])=[CH:6][CH:7]=1)=[O:24]

Participants

4

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 577868(4-Amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone

Product 1

HCID 684296572-chloro-N-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-acetamideYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4-amino-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone (3.0 g, 11.01 mmol) and TEA (3.1 ml, 22.03 mmol) in dry THF (100 ml) was added dropwise chloroacetyl chloride (1.05 ml, 13.22 mmol). The mixture was stirred for 75 min. and evaporated followed by addition of water 75 (ml). The aqueous phase was extracted with EtOAc (2×50 ml) and the combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The resulting residue was dissolved in EtOAc (40 ml) and filtered through a 2.5 cm path of silicagel. The filtrated was evaporated to dryness affording 3.3 g (86%) of 2-chloro-N-[4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]-acetamide as an oil.

Workup

  1. customevaporated
  2. additionfollowed by addition of water 75 (ml)
  3. extractionThe aqueous phase was extracted with EtOAc (2×50 ml)
  4. dry with materialthe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. dissolutionThe resulting residue was dissolved in EtOAc (40 ml)
  8. filtrationfiltered through a 2.5 cm path of silicagel
  9. customThe filtrated was evaporated to dryness

Sources & evidence

ORD record
ord-41a1f22999314d96ac7d3e232eec7c2b
Source dataset
uspto-grants-2010_04
Patent number
US07700583B2

Reaction notes

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