Phenylacetaldehyde → (S)-3-Phenylethylamino-2-oxo-1-piperidineacetic acid, benzyl ester hydrochloride

HRID 1636513Notes

Reaction equation

HRID 1636513 reaction equation
[ClH:1].[NH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([CH2:9][C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[C:4]1=[O:20].[C:21]1([CH2:27][CH:28]=O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[ClH:1].[C:21]1([CH2:27][CH2:28][NH:2][C@H:3]2[CH2:8][CH2:7][CH2:6][N:5]([CH2:9][C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[C:4]2=[O:20])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 998PhenylacetaldehydeHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 70271136(S)-Benzyl 2-(3-amino-2-oxopiperidin-1-yl)acetate hydrochloride

Product 1

HCID 86755206(S)-3-Phenylethylamino-2-oxo-1-piperidineacetic acid, benzyl ester hydrochlorideYield 66%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of 41 (1.50 g, 5.02 mmol) and phenylacetaldehyde (0.724 g, 6.03 mmol) in 35 mL of 1, 2-dichloroethane was added triethylamine (2.03 g, 21.1 mmol, 2.80 mL). After stirring at ambient temperature for 10 min, sodium triacetoxyborohydride (1.49 g, 7.03 mmol) was added rapidly over a 5 min period. The reaction mixture was stirred at room temperature for 15 hrs and quenched with 30 mL of water. The mixture was diluted with 50 mL of CH2Cl2 and the organic phase was separated, washed with 30 mL portions of saturated NaHCO3, water, brine, dried over MgSO4, filtered, and evaporated. The residue was purified by flash chromatography on silica gel eluting with CH2C12, ethanol: 95, 5 to afford 1.21 g (66% yield) of product 42 as a pale yellow oil; TLC (silica gel; CH2Cl2, ethanol: 9, 1): Rf=0.4

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 15 hrs
  2. customquenched with 30 mL of water
  3. additionThe mixture was diluted with 50 mL of CH2Cl2
  4. customthe organic phase was separated
  5. washwashed with 30 mL portions of saturated NaHCO3, water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash chromatography on silica gel eluting with CH2C12, ethanol

Sources & evidence

ORD record
ord-d4ba04ab414b41ba965faf207390f43b
Source dataset
uspto-grants-2000_03
Patent number
US06034215

Reaction notes

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