4-tert-Butylbenzaldehyde → HCID 70222481, compound

HRID 568092Notes

Reaction equation

HRID 568092 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].[C:26]([C:30]1[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][CH:31]=1)([CH3:29])([CH3:28])[CH3:27].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>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]([NH:2][CH2:34][C:33]2[CH:36]=[CH:37][C:30]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:31][CH:32]=2)[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

7

Reactant 4

HCID 703244-tert-ButylbenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 69584616(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride

Product 1

HCID 70222481HCID 70222481, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (3.85 g, 10.6 mmol, Example 2, Step A) and 4-tert-butylbenzaldehyde (1.72 g, 10.6 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (54 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 (3.37 g, 15.9 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 (77 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. The solution was concentrated in vacuo affording a viscous oil. Title compound was isolated by flash chromatography (30% EtOAc in hexanes). The free amine was dissolved in 20 mL of ethyl ether and treated with ethereal HCl to afford 1.71 g (34%) of the pure titled compound as a white foam; mp 95-105° 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-073dda136cff4553970fcb7d98a6ef8d
Source dataset
uspto-grants-2001_01
Patent number
US06180677B2

Reaction notes

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