Tetrahydrofuran → N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine tartrate hemihydrate

HRID 2111917Notes

Reaction equation

HRID 2111917 reaction equation
[CH3:1][CH:2]([CH3:19])[CH2:3][N:4]([CH2:11][C:12]1[S:16][C:15]([Cl:17])=[N:14][C:13]=1[Cl:18])[CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[C:20]([OH:29])(=[O:28])[C@@H:21]([C@H:23]([C:25]([OH:27])=[O:26])[OH:24])[OH:22].C1COCC1>O>[OH2:22].[C:25]([CH:23]([CH:21]([C:20]([OH:29])=[O:28])[OH:22])[OH:24])([OH:27])=[O:26].[CH3:1][CH:2]([CH3:19])[CH2:3][N:4]([CH2:11][C:12]1[S:16][C:15]([Cl:17])=[N:14][C:13]=1[Cl:18])[CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[CH3:1][CH:2]([CH3:19])[CH2:3][N:4]([CH2:11][C:12]1[S:16][C:15]([Cl:17])=[N:14][C:13]=1[Cl:18])[CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[C:25]([CH:23]([CH:21]([C:20]([OH:29])=[O:28])[OH:22])[OH:24])([OH:27])=[O:26]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 444305L-Tartaric acidHCID 57640332N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine

Product 1

HCID 131727425N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine tartrate hemihydrateYield 127.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine (193.6 g, 0.6 mol) in 2 L THF at 65° C. are added seed crystals and L-tartaric acid (90.15 g, 0.6 mol, 1 equiv.) solution in 100 ml water dropwise over 5 min (after 15 min the solution becomes turbid and the product begins to crystallize). After 3 h at 64° C., the mixture is cooled down to room temperature, and then stirred for an additional 20 h. The reaction mixture is then cooled down to 10° C. and filtered; the solid is washed with cold THF/water 95/5 and dried under vacuum to afford 245.8 g of N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine tartrate hemihydrate (87% yield). 1H NMR (250 MHz, DMSO d6): δ=3.97 (2H, s), 3.69 (2H, s), 3.24 (2H, brd), 2.77 (3H, m), 2.20 (2H, d), 1.63 (5H, m), 0.80 (6H, d); 13C NMR (62 MHz, DMSO d6): δ=175.09, 149.48, 138.32, 131.24, 72.39, 58.12, 55.08, 47.04, 43.29, 26.72, 24.60, 20.81.

Workup

  1. customto crystallize)
  2. temperatureThe reaction mixture is then cooled down to 10° C.
  3. filtrationfiltered
  4. washthe solid is washed with cold THF/water 95/5
  5. customdried under vacuum

Sources & evidence

ORD record
ord-542f2e4d9923422f9b0c6a0ea7868b90
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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