Hydrochloric Acid → HCID 70218167, compound

HRID 430810Notes

Reaction equation

HRID 430810 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].[CH3:26][C:27]([CH3:32])([CH3:31])[CH2:28][CH:29]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].Cl>C(Cl)Cl.C(OCC)C.CCOC(C)=O>[ClH:1].[CH2:19]([O:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][C@H:3]([NH:2][CH2:29][CH2:28][C:27]([CH3:32])([CH3:31])[CH3:26])[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 5

HCID 313Hydrochloric AcidHCID 763353,3-DimethylbutanalHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 69584616(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride

Product 1

HCID 70218167HCID 70218167, compoundYield 60.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (1.74 g, 4.80 mmol, Example 2, Step A) and 3,3-dimethylbutyraldehyde (0.48 g, 4.8 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (24 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 (1.53 g, 7.20 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 (24 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 (2×25 mL). The combined organic solution was dried over Na2SO4. TLC (50% EtOAc in Hexanes as the eluant) showed two spots with Rf values 0.87 and 0.39. The solution was concentrated in vacuo affording a viscous oil. The lower spot on the TLC (Rf=0.39) was isolated by flash chromatography (40% EtOAc in hexanes). The free amine was dissolved in 20 mL of ethyl ether and treated with ethereal HCl to afford 1.29 g (60%) of the pure titled compound as a white solid; mp 238-240° 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 (2×25 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-20b370d38e7944169c96e6b45686936d
Source dataset
uspto-grants-2001_11
Patent number
US06323243B1

Reaction notes

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