Triethylamine → 2-Bromo-N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)acetamide

HRID 1618807Notes

Reaction equation

HRID 1618807 reaction equation
[CH3:1][C:2]1([CH3:26])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH2:11][NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[O:3]1.C(N(CC)CC)C.[Br:34][CH2:35][C:36](Cl)=[O:37]>C(Cl)Cl>[Br:34][CH2:35][C:36]([N:12]([CH2:11][C:10]1[C:4]2[O:3][C:2]([CH3:26])([CH3:1])[CH2:6][C:5]=2[CH:7]=[CH:8][CH:9]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:37]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 89602Bromoacetyl chloride2×HCID 67257445N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)amine

Product 1

HCID 672575562-Bromo-N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)acetamideYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)amine (0.20 g, 0.58 mmol) dissolved in DCM (2 mL) was added triethylamine (0.24 g, 2.32 mmol, 0.32 mL). The reaction was cooled to 0° C. and bromoacetyl chloride (0.18 g, 1.16 mmol, 0.10 mL) was added. The mixture was stirred at room temperature for 2 h. LC-MS indicated starting material and product (1:1). Further triethylamine (0.24 g, 2.32 mmol, 0.32 mL) and bromoacetyl chloride (0.18 g, 1.16 mmol, 0.10 mL) were added and stirred at room temperature for 2 h. The solvents were removed in vacuo, the residue quenched with water (10 mL), extracted with DCM (2×20 mL), dried over MgSO4, filtered and solvents removed in vacuo. The crude material was purified by silica gel chromatography eluting with petroleum spirit (A) and EtOAc (B) (30% B, 80 g, 2.5 CV, 60 mL/min). The impure product was further purified by silica gel chromatography eluting with DCM (A) and EtOAc (B) (1-5% B, 80 g, 5 CV, 60 mL/min) to afford 170 mg (63%) of 2-Bromo-N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)acetamide as a colourless oil.

Workup

  1. stirringstirred at room temperature for 2 h
  2. customThe solvents were removed in vacuo
  3. customthe residue quenched with water (10 mL)
  4. extractionextracted with DCM (2×20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customsolvents removed in vacuo
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with petroleum spirit (A) and EtOAc (B) (30% B, 80 g, 2.5 CV, 60 mL/min)
  10. customThe impure product was further purified by silica gel chromatography
  11. washeluting with DCM (A) and EtOAc (B) (1-5% B, 80 g, 5 CV, 60 mL/min)

Sources & evidence

ORD record
ord-755b0c737c4742829060c2a45c67280e
Source dataset
uspto-grants-2014_07
Patent number
US08771641B2

Reaction notes

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