Hydrochloric Acid → (S)-3-(4-Benzyloxy-phenyl)-2-[bis-(3-methyl-butyl)-amino]-N-tert-butyl-propionamide monohydrochloride

HRID 430807Notes

Reaction equation

HRID 430807 reaction equation
[ClH:1].[NH2:2][C@@H:3]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)[C:4]([NH:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[CH:26](=O)[CH2:27][CH:28]([CH3:30])[CH3:29].C(O[BH-](O[C:42](=O)[CH3:43])OC(=O)C)(=O)C.[Na+].[C:46]([O-])(O)=O.[Na+].Cl.[CH2:52](OCC)[CH3:53]>C(Cl)Cl.CCOC(C)=O>[ClH:1].[CH2:19]([O:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][C@H:3]([N:2]([CH2:52][CH2:53][CH:42]([CH3:43])[CH3:46])[CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[C:4]([NH:6][C:7]([CH3:8])([CH3:10])[CH3:9])=[O:5])=[CH:17][CH:16]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 115523-MethylbutanalHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 69584616(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride

Product 1

HCID 70220410(S)-3-(4-Benzyloxy-phenyl)-2-[bis-(3-methyl-butyl)-amino]-N-tert-butyl-propionamide monohydrochlorideYield 10%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (5.0 g, 14 mmol, Example 2, Step A) and isovaleraldehyde (1.5 mL, 14 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (70 mL). After stirring at ambient temperature under a nitrogen atmosphere for 30 minutes, the solution was cooled to 0° C. in an ice-water bath. To this solution was added sodium triacetoxyborohydride (4.4 g, 21 mmol). The resulting reaction mixture was stirred for 30 minutes at 0° C., followed by an additional 12 hours at ambient temperature. Saturated aqueous NaHCO3 solution (100 mL) 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 (2×70 mL). The combined organic solution was dried over Na2SO4. TLC (70% EtOAc in Hexanes as the eluant) showed two spots with Rf values of 0.84 and 0.51. The solution was concentrated in vacuo affording a viscous oil. The higher spot on the TLC (Rf=0.84) was isolated by flash chromatography (50% EtOAc in hexanes). The free amine was dissolved in 10 mL of ethyl ether and treated with ethereal HCl to afford 0.70 g (10%) of the pure titled compound as a white solid; mp 50-60° C.

Workup

  1. temperaturethe solution was cooled to 0° C. in an ice-water bath
  2. customThe resulting reaction mixture
  3. stirringwas stirred for 30 minutes at 0° C.
  4. waitfollowed by an additional 12 hours at ambient temperature
  5. stirringthe resulting mixture was stirred for 5 minutes
  6. customThe two layers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (2×70 mL)
  8. dry with materialThe combined organic solution was dried over Na2SO4
  9. concentrationThe solution was concentrated in vacuo
  10. customaffording a viscous oil

Sources & evidence

ORD record
ord-1fc147a3adfe4d6497b82b2511ce85cd
Source dataset
uspto-grants-2001_11
Patent number
US06323243B1

Reaction notes

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