Acetic Anhydride → 4-(2-Acetoxy-ethyl)-4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 599464Notes

Reaction equation

HRID 599464 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([S:20][C:21]2[CH:26]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24]([OH:31])=[C:23]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:22]=2)([CH2:14][C:15](OCC)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].C(N(CC)CC)C.[CH3:49][C:50](OC(C)=O)=[O:51]>C1COCC1.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([CH2:14][CH2:15][O:16][C:50](=[O:51])[CH3:49])([S:20][C:21]2[CH:22]=[C:23]([C:32]([CH3:35])([CH3:33])[CH3:34])[C:24]([OH:31])=[C:25]([C:27]([CH3:28])([CH3:29])[CH3:30])[CH:26]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 21226445Aluminium lithium hydrideHCID 866354214-(3,5-Di-tert-butyl-4-hydroxy-phenylsulfanyl)-4-ethoxycarbonylmethyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866354224-(2-Acetoxy-ethyl)-4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl esterYield 82.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-4-ethoxycarbonylmethyl-piperidine-1-carboxylic acid tert-butyl ester (Ex. 1a, 510 mg, 1 mmol) in 4 mL of THF was added dropwise 1 M LiAlH4 solution (4 mL, 4 mmol) over a period of 15 min. The reaction was stirred for 1 h and then quenched with saturated NH4Cl solution (30 mL). The mixture was extracted with Ethyl acetate (40+20 mL) and the combined organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in 8 mL of dichloromethane. Triethylamine (300 mg, 2.9 mmol) and DMAP (10 mg) were added followed by dropwise addition of Ac2O (205 mg, 2 mmol). The reaction mixture was stirred for 3 h and then diluted with Ethyl acetate (40 mL). The mixture was washed with 1 N HCl (2×30 mL) and water (50 mL) and dried over Na2SO4. Chromatography (2-20% Ethyl acetate/hexanes) afforded 4-(2-acetoxy-ethyl)-4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester as a clear oil (420 mg, 82%). ESI/CI-MS m/z 506 ([M−H]−).

Workup

  1. customquenched with saturated NH4Cl solution (30 mL)
  2. extractionThe mixture was extracted with Ethyl acetate (40+20 mL)
  3. dry with materialthe combined organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 8 mL of dichloromethane
  6. stirringThe reaction mixture was stirred for 3 h
  7. washThe mixture was washed with 1 N HCl (2×30 mL) and water (50 mL)
  8. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-1c85f102a62643238a97dc58ef9698f7
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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