Diethyl Ether → [3-(4-Chlorophenyl)-1-[(3-chlorophenyl)-methyl]-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl]-morpholin-4-yl-methanone

HRID 623759Notes

Reaction equation

HRID 623759 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH3:13])=[C:11]([C:14]([F:17])([F:16])[F:15])[NH:10][C:9]=2[C:18]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:19])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Cl:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH2:36]Br.CCOCC>CC#N.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH3:13])=[C:11]([C:14]([F:15])([F:16])[F:17])[N:10]([CH2:36][C:35]3[CH:38]=[CH:39][CH:40]=[C:33]([Cl:32])[CH:34]=3)[C:9]=2[C:18]([N:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)=[O:19])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 86711843(3-(4-Chlorophenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone

Product 1

HCID 73296604[3-(4-Chlorophenyl)-1-[(3-chlorophenyl)-methyl]-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl]-morpholin-4-yl-methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

(3-(4-Chlorophenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone (80 mg, 0.215 mmol) was dissolved in dry MeCN (5 mL). The solution was mixed with K2CO3 (59 mg, 0.429 mmol), followed by addition of 3-chlorobenzyl bromide (31 μL, 0.236 mmol). The reaction mixture was stirred vigorously at 80° C. overnight. The temperature was lowered to room temperature; the reaction mixture was combined with a few lumps of ice, Et2O (50 mL) and H2O (10 mL) to result in a clear two phase system. The phases were separated; the organic phase was washed with brine. Drying (Na2SO4) was followed by concentration in vacuo. The residue was dissolved in MeCN (30 mL), concentrated in vacuo and used for preparative TLC (silica, heptane/EtOAc, 5:1), providing 96 mg (90%) of SC-25 as a fluffy white solid.

Workup

  1. customwas lowered to room temperature
  2. customto result in a clear two phase system
  3. customThe phases were separated
  4. washthe organic phase was washed with brine
  5. dry with materialDrying (Na2SO4)
  6. concentrationwas followed by concentration in vacuo
  7. dissolutionThe residue was dissolved in MeCN (30 mL)
  8. concentrationconcentrated in vacuo
  9. customproviding 96 mg (90%) of SC-25 as a fluffy white solid

Sources & evidence

ORD record
ord-f69ae03393fd4465b647259a0e9ae583
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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