2-Aminothiazole → 4-Cyclohexyl-4-(thiazol-2-ylaminomethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1795172Notes

Reaction equation

HRID 1795172 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)([CH:14]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)([CH2:14][NH:22][C:23]2[S:24][CH:25]=[CH:26][N:27]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 21552-AminothiazoleHCID 5049666Sodium triacetoxyborohydrideHCID 219368754-Cyclohexyl-4-formylpiperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 210237784-Cyclohexyl-4-(thiazol-2-ylaminomethyl)-piperidine-1-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Cyclohexyl-4-formyl-piperidine-1-carboxylic acid tert-butyl ester, 3, (296 mg, 1.0 mmol) and 2-aminothiazole (103 mg, 1.0 mmol) are dissolved in toluene (15 mL), and the mixture was refluxed using a Dean-Stark apparatus overnight. The solution is then cooled to room temperature and sodium triacetoxyborohydride added. The reaction is stirred at room temperature for three hours and then diluted with ethyl acetate. The reaction mixture is washed with aqueous sodium bicarbonate and brine. The solvent is removed under reduced pressure and the residue purified by preparative HPLC to afford 312 mg (82% yield) of the desired compound. MS (ESI) m/z 380 (M+H+)

Workup

  1. temperaturethe mixture was refluxed
  2. customa Dean-Stark apparatus overnight
  3. washThe reaction mixture is washed with aqueous sodium bicarbonate and brine
  4. customThe solvent is removed under reduced pressure
  5. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-33eec37674764f2fa0152207c7eb01cc
Source dataset
uspto-grants-2006_04
Patent number
US07026335B2

Reaction notes

Loading…