Potassium Carbonate → [3-(4-Chlorophenyl)-1-[2-(4-fluoro-phenoxy)-ethyl]-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl]-morpholin-4-yl-methanone

HRID 623767Notes

Reaction equation

HRID 623767 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+].[F:32][C:33]1[CH:42]=[CH:41][C:36]([O:37][CH2:38][CH2:39]Br)=[CH:35][CH:34]=1>CC#N>[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]([CH2:39][CH2:38][O:37][C:36]3[CH:41]=[CH:42][C:33]([F:32])=[CH:34][CH:35]=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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 20641711-(2-Bromoethoxy)-4-fluorobenzeneHCID 86711843(3-(4-Chlorophenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone2×

Product 1

HCID 73297074[3-(4-Chlorophenyl)-1-[2-(4-fluoro-phenoxy)-ethyl]-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl]-morpholin-4-yl-methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

(3-(4-Chlorophenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone [for synthesis see SC-25] (130 mg, 0.349 mmol) was dissolved in dry MeCN (4 mL). The solution was mixed with K2CO3 (120 mg, 0.872 mmol) and KI (8.7 mg, 0.052 mmol), followed by addition of 4-fluorophenoxy-ethylbromide (153 mg, 0.697 mmol). The reaction mixture was stirred vigorously at 80° C. for 2 d. The temperature was lowered to room temperature; the reaction mixture was combined with the reaction mixture of another identical reaction (starting from 20 mg or 0.054 mmol (3-(4-chlorophenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone), followed by concentration in vacuo. The residue was used for flash chromatography (silica, gradient heptane/EtOAc, 1:0→1:1). The product was purified by preparative TLC (silica, DCM twice) to result in 60 mg (29%) of SC-51.

Workup

  1. customwas lowered to room temperature
  2. concentrationfollowed by concentration in vacuo
  3. customThe product was purified by preparative TLC (silica, DCM twice)
  4. customto result in 60 mg (29%) of SC-51

Sources & evidence

ORD record
ord-709f6589ab2a4993a45e8d79ddfd84ca
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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