p-tert-Butoxybenzaldehyde → HCID 23388392, compound

HRID 990386Notes

Reaction equation

HRID 990386 reaction equation
[NH2:1][C@@H:2]([CH2:26][CH:27]([CH3:29])[CH3:28])[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].[C:30]([O:34][C:35]1[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=1)([CH3:33])([CH3:32])[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[F:18][C:15]1[CH:14]=[CH:13][C:12]([CH:11]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[N:8]2[CH2:7][CH2:6][N:5]([C:3](=[O:4])[C@@H:2]([NH:1][CH2:39][C:38]3[CH:41]=[CH:42][C:35]([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:36][CH:37]=3)[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:10][CH2:9]2)=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 93774p-tert-ButoxybenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12017817HCID 12017817, compound

Product 1

HCID 23388392HCID 23388392, compoundYield 44.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-1-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}4-methyl-pentan-1-one (0.500 g, 1.25 mmol, Example 53) and 4-(tert-butoxy)benzaldehyde (0.229 mL, 1.25 mmol, Lancaster) 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 (0.396 g, 1.87 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 25 minutes. The 2 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 0.9 and 0.55. The solution was concentrated in vacuo affording a viscous oil. The lower spot on TLC (Rf=0.55) was isolated by flash chromatography (30% EtOAc in hexanes). Forty-four percent (0.311 g) of the pure titled compound was obtained as a white foam: mp 56-61° C. APCI-MS m/z 564.5 (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 25 minutes
  7. customThe 2 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-d9772ffd93dd4549bdf3fb5d85da2455
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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