Lithium Hexamethyldisilazide → 4-[2-(tert-Butyldimethylsilyloxy)-1-hydroxyethyl]-piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-ethyl ester

HRID 746996Notes

Reaction equation

HRID 746996 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Si:32]([O:39][CH2:40][CH:41]=[O:42])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1([CH:41]([OH:42])[CH2:40][O:39][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:7][CH2:8][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 152896721-Benzyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 691457314-[2-(tert-Butyldimethylsilyloxy)-1-hydroxyethyl]-piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-ethyl esterYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of piperidine-1,4-dicarboxylic acid 1-benzyl ester 4-ethyl ester (Description 1; 10 g, 34.4 mmol) in tetrahydrofuran (100 ml) was cooled to −78° C. Lithium bis(trimethylsilyl)amide (1.0M in tetrahydrofuran, 50 ml, 50 mmol) was added dropwise and the mixture stirred, allowing to warm to room temperature over 1.5 hours. The orange solution was re-cooled to −78° C. and (tert-butyldimethylsilyloxy)acetaldehyde (10 g, 57.3 mmol) added. The mixture was allowed to warm to room temperature over 2.5 hours, then quenched with saturated aqueous ammonium chloride solution. The reaction mixture was partitioned between diethyl ether and water. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 5-15% diethyl ether/dichloromethane, to give the title compound (12.4 g, 78%).

Workup

  1. temperatureThe orange solution was re-cooled to −78° C.
  2. temperatureto warm to room temperature over 2.5 hours
  3. customquenched with saturated aqueous ammonium chloride solution
  4. customThe reaction mixture was partitioned between diethyl ether and water
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica
  8. washeluting with 5-15% diethyl ether/dichloromethane

Sources & evidence

ORD record
ord-ab110aca7c3046fe8c5eab48f71bf9d7
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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