Benzene → (R)-6-(tert-butyldimethylsilanyloxymethyl)-piperidin-2-one

HRID 349309Notes

Reaction equation

HRID 349309 reaction equation
N1C=CN=C1.[Si:6](Cl)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[OH:14][CH2:15][C@@H:16]1[NH:21][C:20](=[O:22])[CH2:19][CH2:18][CH2:17]1.C1C=CC=CC=1>CN(C=O)C.CCOC(C)=O>[Si:6]([O:14][CH2:15][C@@H:16]1[NH:21][C:20](=[O:22])[CH2:19][CH2:18][CH2:17]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 241BenzeneHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 10887932(6R)-6-(hydroxymethyl)piperidin-2-one

Product 1

HCID 58635302(R)-6-(tert-butyldimethylsilanyloxymethyl)-piperidin-2-oneYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Imidazole (773 mg, 11.4 mmol) and tert-butyldimethylsilyl chloride (787 mg, 5.22 mmol) were added sequentially to a solution of (R)-6-hydroxymethyl-piperidin-2-one (prepared from D-α-aminoadipic acid according to Huang, et al., Synth. Commun. 1989, 19, 3485–3496, 613 mg, 4.75 mmol) in DMF (8 mL) at 0° C. The reaction mixture was allowed to warm to rt and was stirred at rt for 20 h. Benzene and EtOAc (3:7, 200 mL) was added and the solution was washed with brine (3×50 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient) afforded 1.13 g (98%) of (R)-6-(tert-butyldimethylsilanyloxymethyl)-piperidin-2-one as a white solid.

Workup

  1. washthe solution was washed with brine (3×50 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-70eabfeb51e94435b5bb4025f5741dfc
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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