Dimethyl Sulfide → tert-butyl (2R)-2-(hydroxymethyl)piperidine-1-carboxylate

HRID 332965Notes

Reaction equation

HRID 332965 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].S(C)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 688618(2R)-1-[(tert-butoxy)carbonyl]piperidine-2-carboxylic acid

Product 1

HCID 6933953tert-butyl (2R)-2-(hydroxymethyl)piperidine-1-carboxylateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 15 g, 18.5 g, 80.7 mmol) in anhydrous THF (44.4 mL) was cooled to 0° C. BH3.Me2S (44.4 mL, 88.8 mmol) was added drop wise over 15 minutes. After complete addition, the mixture was allowed to warm to room temperature, and stirring was continued for 18 hours. The mixture was quenched with water, and extracted with ethyl acetate. The organic extract was dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was flash chromatographed on silica gel (35% ethyl acetate in hexanes) to provide (R)-tert-butyl-2-(hydroxymethyl)piperidine-1-carboxylate as a white solid (14.2 g, 82%). MS 116 (MH+-boc)

Workup

  1. customwas cooled to 0° C
  2. additionAfter complete addition
  3. customThe mixture was quenched with water
  4. extractionextracted with ethyl acetate
  5. extractionThe organic extract
  6. dry with materialwas dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel (35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-07dfb0f5197c48ef9701231bdd9347df
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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