Hydrochloric Acid → HCID 70075633, compound

HRID 990381Notes

Reaction equation

HRID 990381 reaction equation
[NH2:1][C@@H:2]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([CH:11]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)=[O:4].[CH:33](=O)[CH2:34][CH:35]([CH3:37])[CH3:36].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].[ClH:58]>C(Cl)Cl.C(OCC)C.CCOC(C)=O>[ClH:58].[ClH:58].[F:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[N:8]2[CH2:7][CH2:6][N:5]([C:3](=[O:4])[C@@H:2]([NH:1][CH2:33][CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:10][CH2:9]2)=[CH:17][CH:16]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 115523-MethylbutanalHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12017816HCID 12017816, compound

Product 1

HCID 70075633HCID 70075633, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-1-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-3-phenyl-propan-1-one (0.500 g, 1.15 mmol, Example 52) and isovaleraldehyde (0.123 mL, 1.15 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (6 mL). After stirring at ambient temperature under nitrogen atmosphere for 30 minutes, the solution was cooled to 0° C. in an ice-water bath. To this solution was added sodium triacetoxyborohydride (0.365 g, 1.72 mmol). The resulting reaction mixture was stirred for, in succession, 30 minutes at 0° C. and 12 hours at ambient temperature. Twenty milliliters of saturated aqueous NaHCO3 solution was added to the reaction mixture and the resulting mixture was stirred for 5 minutes. The two layers were separated and the aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic solution was dried over Na2SO4. TLC (50% EtOAc in Hexanes as the eluant) showed two spots with Rf values 1.0 and 0.29. The solution was concentrated in vacuo affording a viscous oil. The lower spot on TLC (Rf=0.29) was isolated by flash chromatography (60% EtOAc in hexanes). The free amine was dissolved in 5 mL of ethyl ether and treated with ethereal HCl to afford 138 mg (20%) of the pure titled compound as a white foam: mp 172-186° C. APCI-MS m/z 506.4 (MH+).

Workup

  1. temperaturethe solution was cooled to 0° C. in an ice-water bath
  2. customThe resulting reaction mixture
  3. stirringwas stirred for, in succession, 30 minutes at 0° C.
  4. custom12 hours
  5. customat ambient temperature
  6. stirringthe resulting mixture was stirred for 5 minutes
  7. customThe two layers were separated
  8. extractionthe aqueous layer was extracted with CH2Cl2 (2×20 mL)
  9. dry with materialThe combined organic solution was dried over Na2SO4
  10. concentrationThe solution was concentrated in vacuo
  11. customaffording a viscous oil

Sources & evidence

ORD record
ord-7e041d057e59454c8c785a26aac7f821
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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