Chloroacetyl chloride → 2-chloro-N-[2-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxoethyl]-acetamide

HRID 644064Notes

Reaction equation

HRID 644064 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](=[O:22])[C:20]#[N:21])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:23][CH2:24][C:25](Cl)=[O:26].C(N(CC)CC)C>C(O)(=O)C.[Pd].ClCCl>[Cl:23][CH2:24][C:25]([NH:21][CH2:20][C:19]([C:10]1[C:11]2[C:16](=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][CH:12]=2)[N:8]([CH2:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH:9]=1)=[O:22])=[O:26]

Participants

7

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 86613200(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile

Product 1

HCID 687020002-chloro-N-[2-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxoethyl]-acetamideYield 75.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-oxoacetonitrile (prepared as described in Example 28; 2.39 g, 8.06 mmol) in acetic acid (50 ml) under nitrogen was added 10% palladium on charcoal (240 mg). The reaction was placed under a hydrogen atmosphere and stirred overnight. The reaction mixture was then filtered through a pad of dicalite. The dicalite was washed with acetic acid and the combined filtrate evaporated to leave a red oil. The red oil was taken up in dichloromethane (50 ml) and to this was added chloroacetyl chloride (0.77 ml, 9.67 mmol) followed by triethylamine (3.4 ml, 24.2 mmol) dropwise. The reaction was stirred for 30 minutes and poured into a separating funnel. The organics were washed sequentially with 5% aqueous sodium carbonate (2×30 ml) and brine (30 ml). The organics were dried over magnesium sulfate, filtered and the solvent removed in vacuo to leave a red/brown oil. The oil was purified by flash chromatography using 20-100% (v/v) dichloromethane in heptane followed by 25-50% (v/v) diethyl ether in heptane to afford 2-chloro-N-[2-(1-cyclohexylmethyl-7-methoxy-1H-indol-3-yl)-2-oxoethyl]-acetamide (2.32 g, 6.1 mmol).

Workup

  1. filtrationThe reaction mixture was then filtered through a pad of dicalite
  2. washThe dicalite was washed with acetic acid
  3. customthe combined filtrate evaporated
  4. customto leave a red oil
  5. stirringThe reaction was stirred for 30 minutes
  6. additionpoured into a separating funnel
  7. washThe organics were washed sequentially with 5% aqueous sodium carbonate (2×30 ml) and brine (30 ml)
  8. dry with materialThe organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. customto leave a red/brown oil
  12. customThe oil was purified by flash chromatography

Sources & evidence

ORD record
ord-ba0d1fb83dc84f159c81d44d91d4b04a
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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