Sodium Bicarbonate → Cinacalcet Hydrochloride

HRID 476316Notes

Reaction equation

HRID 476316 reaction equation
Cl.[Cl:2][C@@H:3]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=1)[CH2:4][CH2:5][NH:6][CH:7]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)[CH3:8].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:8][C@@H:7]([NH:6][CH2:5][CH2:4][CH2:3][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=12.[ClH:2]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86671130HCID 86671130, compound

Product 1

HCID 156418Cinacalcet HydrochlorideYield 82.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

(R)-3-chloro-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydro-chloride (X) (15.0 g, 35.021 mmol) is suspended in toluene (90 ml) at 15°-20° C. and sat. aq. sodium bicarbonate (75.6 g, X72 mmol) is charged drop-wise, under vigorous stirring, until pH=8-9 of the aqueous layer. The mixture is layered upon standing few minutes and then the organic phase is separated, washed with water (2×75 ml) and transferred into an autoclave. 5% Palladium on carbon (50% moisture content) is added (0.373 g, 0.088 mmol), followed by methanol (15 ml), the mixture is exposed to inert atmosphere, then pressurized with 100 kPa hydrogen gas, upon stirring at 20° C. Hydrogen pressure is maintained until positive IPC (via HPC, about 4-5 hrs), then the reaction mixture is filtered through a Celite® pad. Methanol is distilled off the filtered solution and isopropyl acetate (IPAC) (90 ml) is added. The resulting suspension is heated up to 70° C. and stirred for 30 minutes, then cooled down slowly to 0° C. Cinacalcet hydrochloride is isolated as a white powder upon filtration, washing with IPAC (2×15 ml) and exsiccation at 60*-65° C. under vacuum (11.4 g, 28.944 mmol; yield: 82.6%).

Workup

  1. waitupon standing few minutes
  2. customthe organic phase is separated
  3. washwashed with water (2×75 ml)
  4. addition5% Palladium on carbon (50% moisture content) is added (0.373 g, 0.088 mmol)
  5. temperatureHydrogen pressure is maintained until positive IPC (via HPC, about 4-5 hrs)
  6. filtrationthe reaction mixture is filtered through a Celite® pad
  7. distillationMethanol is distilled off the filtered solution and isopropyl acetate (IPAC) (90 ml)
  8. additionis added
  9. temperatureThe resulting suspension is heated up to 70° C.
  10. stirringstirred for 30 minutes
  11. temperaturecooled down slowly to 0° C

Sources & evidence

ORD record
ord-2c63a08ff68b4b24a1c9a713db230484
Source dataset
uspto-grants-2014_01
Patent number
US08637708B2

Reaction notes

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