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Dimethyl Sulfide → (R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 451953
Notes
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Reaction equation

HRID 451953 reaction equation
S(C)C.C1(C)C=CC=CC=1.[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:33])=[C:16]([CH:32]=1)[C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]1)=[O:18]>C1COCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:33])=[C:16]([C@H:17]([OH:18])[C@@H:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:20]2)[CH:32]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 1140TolueneHCID 58011514(R)-tert-butyl 3-(5-chloro-2-methylbenzoyl)piperidine-1-carboxylate

Product 1

HCID 58011541(R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-15 °C

Procedure

A mixture of 10 M BH3.Me2S in THF (25.4 mL, 0.254 mol) and 1 M R-CBS-oxazaborolidine in toluene (38 mL, 0.038 mol) were dissolved in 100 mL anhydrous THF and cooled to −15° C. (R)-tert-butyl 3-(5-chloro-2-methylbenzoyl)piperidine-1-carboxylate in 200 mL anhydrous THF was added dropwise to the above solution and stirred at −15° C. for 2 hr. The reaction was quenched with methanol (300 mL). The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give (R)-tert-butyl 3-((R)-(5-chloro-2-methylphenyl)(hydroxy)methyl)piperidine-1-carboxylate (32 g), which contained 30% isomer.

Workup

  1. additionwas added dropwise to the above solution
  2. customThe reaction was quenched with methanol (300 mL)
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-193c0ec44ab649b59bc75e0394a1b516
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08487108B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes