Hydrochloric Acid → (4-(2-Chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate

HRID 655952Notes

Reaction equation

HRID 655952 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][NH:5][C:6]([C:8]1([CH2:21][OH:22])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1)=[O:7].[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][C:32]([N:35]=[C:36]=[O:37])=[CH:31][CH:30]=1.Cl>C1COCC1.CN(C1C=CN=CC=1)C.CO>[F:27][C:28]([F:38])([F:39])[C:29]1[CH:30]=[CH:31][C:32]([NH:35][C:36](=[O:37])[O:22][CH2:21][C:8]2([C:6](=[O:7])[NH:5][CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[Cl:1])[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:33][CH:34]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 59778532Tert-butyl 4-(2-chlorobenzylcarbamoyl)-4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 59778560(4-(2-Chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamateYield 100.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(2-chlorobenzylcarbamoyl)-4-(hydroxymethyl)piperidine-1-carboxylate (500 mg, 1.3 mmol), in THF were added DMAP (32 mg, 0.26 mmol, 0.2 equiv.) and 4-trifloromethylphenylisocyanate (0.28 mL, 1.97 mmol, 1.5 equiv.). The reaction mixture was stirred for 1 h. The reaction mixture was concentrated to dryness. To a solution of the above crude mixture in CH3OH (3 mL) was added HCl (4 M in dioxane, 1 mL, 4 mmol, 3 equiv.). The reaction mixture was stirred overnight. The white solid was filtered and dried to give (4-(2-chlorobenzylcarbamoyl)piperidin-4-yl)methyl 4-(trifluoromethyl)phenylcarbamate (615 mg, 93%). LRMS (M-Boc+H+) m/z 470.1.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. stirringThe reaction mixture was stirred overnight
  3. filtrationThe white solid was filtered
  4. customdried

Sources & evidence

ORD record
ord-1149a50cdbe44fd68b9d4ea8d1e1741f
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Reaction notes

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