Triethylamine → 7-(2-Fluorobenzoyl)-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-one

HRID 2164297Notes

Reaction equation

HRID 2164297 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[F:12])=[O:5].CC[C:19](OCC)=[S:20].[C:24]([O:28]Cl)(C)(C)[CH3:25].C(N(CC)CC)C>C(Cl)Cl>[F:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:4]([C:3]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:2]=1[NH:1][C:24](=[O:28])[CH:25]2[S:20][CH3:19])=[O:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 741012-Amino-2'-fluorobenzophenoneHCID 521297Tert-Butyl hypochloriteHCID 12284386Ethyl methylthioacetate

Product 1

HCID 133942837-(2-Fluorobenzoyl)-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-oneYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 86 g (0.4 mole) of 2-amino-2'-fluorobenzophenone in 3 liters of methylene chloride was cooled to -65° C. and 54 g (0.4 mole) of ethyl methylthioacetate was added. A solution of 46 g (0.42 mole) of 95% tertiary butoxy chloride in 100 ml of methylene chloride was added dropwise, keeping the temperature below -65° C. One hour after addition was complete, 41 g (0.4 mole) of triethylamine was added dropwise and the mixture allowed to warm to room temperature. The solution was concentrated to about 1400 ml and then washed with water. The organic solution was concentrated and the residue dissolved in 800 ml methanol containing 60 ml of concentrated hydrochloric acid. The mixture was heated at reflux for one hour followed by cooling. The mixture stood overnight, then the crystals were collected and recrystallized from 20% aqueous ethanol to give 66 g (55%)pale yellow needles; m.p. 147.0°-148.5° C.

Workup

  1. customthe temperature below -65° C
  2. additionOne hour after addition
  3. concentrationThe solution was concentrated to about 1400 ml
  4. washwashed with water
  5. concentrationThe organic solution was concentrated
  6. dissolutionthe residue dissolved in 800 ml methanol containing 60 ml of concentrated hydrochloric acid
  7. temperatureThe mixture was heated
  8. temperatureat reflux for one hour
  9. temperatureby cooling
  10. customthe crystals were collected
  11. customrecrystallized from 20% aqueous ethanol

Sources & evidence

ORD record
ord-ed0c19579f994703af3753e6ad4658b9
Source dataset
uspto-grants-1985_03
Patent number
US04503073

Reaction notes

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