Dimethyl Sulfoxide → tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpiperidine-1-carboxylate

HRID 1644484Notes

Reaction equation

HRID 1644484 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Si:11]([O:18][C@H:19]1[CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@@H:22]([CH2:32][OH:33])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(OCC)(=O)C>[Si:11]([O:18][C@H:19]1[CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@@H:22]([CH:32]=[O:33])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 66773985tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)piperidine-1-carboxylate2×

Product 1

HCID 86630428tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpiperidine-1-carboxylateYield 90.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of oxalyl chloride (2.4 mL) in methylene chloride (75 mL) at −78° C. was slowly added dimethylsulfoxide (3 mL) in methylene chloride (25 mL). After 10 minutes, a solution of tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)piperidine-1-carboxylate (Intermediate 190, 7.60 g) in methylene chloride (40 mL) was slowly added. After 30 minutes at −78° C., diisopropylethylamine (10 mL) was added and the reaction warmed to room temperature. The reaction was diluted with ethyl acetate, washed with 0.5 M HCl, NaHCO3 and brine solutions, dried (Na2SO4), filtered and concentrated. Chromatography on silica gel with a gradient of 0-30% ethyl acetate in hexanes gave 6.84 g of product.

Workup

  1. customat −78° C.
  2. waitAfter 30 minutes at −78° C.
  3. washwashed with 0.5 M HCl, NaHCO3 and brine solutions
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b8c1ed402b534816b28623ff016287b4
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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