4-(Trifluoromethyl)phenyl isocyanate → HCID 25252814, compound

HRID 2063489Notes

Reaction equation

HRID 2063489 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][C:7]2[CH:8]=[N:9][O:10][C:11]=2[C@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17]([O:19]C(C)(C)C)=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[N:35]([C:38]1[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=1)=C=O>Cl.O1CCOCC1.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[CH:8]=[N:9][O:10][C:11]=2[C@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[C:17]([NH:35][C:38]2[CH:43]=[CH:42][C:41]([C:44]([F:45])([F:46])[F:47])=[CH:40][CH:39]=2)=[O:19])=[CH:24][CH:25]=1

Participants

7

Reactant 3

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 81531DiisopropylethylamineHCID 57650417HCID 57650417, compound

Product 1

HCID 25252814HCID 25252814, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-tert-butyl 2-(4-(4-chlorobenzyl)isoxazol-5-yl)pyrrolidine-1-carboxylate (32 mg, 0.9 mmol) was dissolved in 4M HCl in 1,4-dioxane (2 mL), stirred for 2 h and then concentrated in vacuo. The resulting reaction residue was suspended in dicloromethane (2 mL) and DIEA (31 μL, 0.18 mmol) before 1-isocyanato-4-(trifluoromethyl)benzene (25 mg, 0.13 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)isoxazol-5-yl)-N-(4-(trifluoromethyl)phenyl)pyrrolidine-1-carboxamide (19 mg, 47%).

Workup

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

Sources & evidence

ORD record
ord-ab0a6e7fb9534d1199ac551ae306f710
Source dataset
uspto-grants-2012_10
Patent number
US08288371B2

Reaction notes

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