4-(Trifluoromethyl)phenyl isocyanate → HCID 25252969, compound

HRID 2063491Notes

Reaction equation

HRID 2063491 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2[C:8]([C@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18](OC(C)(C)C)=[O:19])=[N:9][N:10]([CH3:12])[CH:11]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[N:36]([C:39]1[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][CH:40]=1)=C=O>Cl.O1CCOCC1>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2[C:8]([C@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([NH:36][C:39]3[CH:44]=[CH:43][C:42]([C:45]([F:46])([F:47])[F:48])=[CH:41][CH:40]=3)=[O:19])=[N:9][N:10]([CH3:12])[CH:11]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 81531DiisopropylethylamineHCID 57650326HCID 57650326, compound

Product 1

HCID 25252969HCID 25252969, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-tert-butyl 2-(4-(4-chlorobenzyl)-1-methyl-1H-pyrazol-3-yl)pyrrolidine-1-carboxylate (39 mg, 0.1 mmol) was dissolved in 4M HCl in 1,4-dioxane (2 mL), stirred for 2 hr and then concentrated in vacuo. The resulting residue was then suspended in dichloromethane (2 mL) and DIEA (34 μL, 0.2 mmol) before 1-isocyanato-4-(trifluoromethyl)benzene (28 μL, 0.15 mmol) was added. After 16 h of stirring, the reaction mixture was concentrated in vacuo. Purification of the resulting residue by silica gel column chromatography (hexanes/ethyl acetate gradient, 10-100% EtOAc) afforded (R)-2-(4-(4-chlorobenzyl)-1-methyl-1H-pyrazol-3-yl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-1-carboxamide (12 mg, 26%).

Workup

  1. concentrationconcentrated in vacuo
  2. stirringAfter 16 h of stirring
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. customPurification of the resulting residue by silica gel column chromatography (hexanes/ethyl acetate gradient, 10-100% EtOAc)

Sources & evidence

ORD record
ord-9dc463904d724646bed907d57573a261
Source dataset
uspto-grants-2012_10
Patent number
US08288371B2

Reaction notes

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