Ammonium Chloride → HCID 57710592, compound

HRID 1928710Notes

Reaction equation

HRID 1928710 reaction equation
[CH3:1][C@@H:2]([NH:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12.C(C1C=C(C(F)(F)F)C=CC=1)#C.CC(C)=[O:41].C(=O)=O.[Li]CCCC.N([C@@H](C1C2C(=CC=CC=2)C=CC=1)C)=C=O.[Cl-].[NH4+]>C1COCC1.CCCCCC>[C:3]1([C@H:2]([NH:13][C:14](=[O:41])[C:15]#[C:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[CH3:1])[C:8]2[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 156419CinacalcetHCID 1706331-(1-Naphthyl)ethyl isocyanateHCID 27784901-Ethynyl-3-(trifluoromethyl)benzeneHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 57710592HCID 57710592, compoundYield 89.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

The invention also provides, in another embodiment, an alternative route for synthesizing cinacalcet via the reduction of an alkyne precursor. The precursor is obtained by reacting an aryl acetylene with an appropriately substituted isocyanate. For example, a solution of 3-ethynyl-α,α,α-trifluorotoluene (0.73 mL; 5.06 mmol; 2.0 equiv.) in anhydrous THF (20 mL) was cooled to −78° C. (acetone/dry ice bath). A hexane solution of n-BuLi (1.6M, 2.69 mL; 4.30 mmol; 1.7 equiv.). is then added and the reaction mixture stirred at −78° C. for 30 minutes. A solution of (R)-1-(1-isocyanatoethyl)naphthalene (1.0 equiv.; 2.53 mmol; 0.447 mL) in THF is then added to the reaction mixture which is stirred for an additional 30 minutes at −78° C. The reaction is stopped by the addition of an aqueous solution of ammonium chloride to the organic mixture. The organic layer is repeatedly extracted with water, dried over magnesium sulfate and the solvent removed in vacuo to afford 3-(3-Trifluoromethyl-phenyl)-propynoic acid ((R)-1-naphthalen-1-yl-ethyl)-amide as product. Isolated 830 mg, 89.2% yield. The identity of the product is confirmed by 1H NMR and high resolution mass spectrometry. (300 MHz, CDCl3) δ ppm 1.77 (d, 3H) 5.97-6.08 (m, 1H) 6.15 (br. S., 1H) 7.42-7.70 (m, 7H) 7.75 (s, 1H) 7.81-7.94 (m, 2H) 8.12 (d, 1H) and HRMS (M+1): 368.1

Workup

  1. customThe invention also provides, in another embodiment
  2. customThe precursor is obtained
  3. customwas cooled to −78° C.
  4. additionis then added
  5. stirringis stirred for an additional 30 minutes at −78° C
  6. extractionThe organic layer is repeatedly extracted with water
  7. dry with materialdried over magnesium sulfate
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-21242e44371b40a9815afe64801baec5
Source dataset
uspto-grants-2012_05
Patent number
US08183415B2

Reaction notes

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