Pentane → (R)-2-Methyl-propane-2-sulfinic acid [(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-propoxy-pyridin-3-yl)-ethyl]-amide

HRID 1908668Notes

Reaction equation

HRID 1908668 reaction equation
C([Li])(C)(C)C.CCCCC.Br[C:12]1[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH3:21])=[N:16][CH:17]=1.[C:22]([Si:26]([CH3:38])([CH3:37])[O:27][CH2:28][CH:29]=[N:30][S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([Si:26]([CH3:38])([CH3:37])[O:27][CH2:28][C@H:29]([NH:30][S@@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])[C:12]1[CH:17]=[N:16][C:15]([O:18][CH2:19][CH2:20][CH3:21])=[CH:14][CH:13]=1)([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 8003PentaneHCID 233940055-Bromo-2-propoxypyridineHCID 86644143(R,E)-N-(2-((tert-butyldimethylsilyl)oxy)ethylidene)-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306, compound

Product 1

HCID 71201913(R)-2-Methyl-propane-2-sulfinic acid [(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-propoxy-pyridin-3-yl)-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.7 M solution of tert-butyllithium in pentane (15.2 mL, 25.8 mmol) was added drop wise to a stirring solution of 5-bromo-2-propoxypyridine IM3 (2.54 g, 11.8 mmol) dissolved in dry THF (29.4 mL) at −78° C. under Ar. The solution was subsequently stirred at this temperature for 30 min. A solution of (R)-2-methyl-propane-2-sulfinic acid [2-(tert-butyl-dimethyl-silanyloxy)ethylidene]-amide IM49 (3.26 g, 11.8 mmol) in dry THF (15 mL) was then added drop wise at −78° C. and the solution was stirred at this temperature for 30 min. The cooling bath was removed and the mixture was allowed to reach room temperature overnight. The mixture was quenched with saturated aqueous NH4Cl solution (75 mL) and EtOAc (150 mL). The phases were separated and the organic layer was washed with brine and then dried over MgSO4. Flash chromatography (silica, 10-100% EtOAc in heptanes) gave (R)-2-Methyl-propane-2-sulfinic acid [(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-(6-propoxy-pyridin-3-yl)-ethyl]amide, the fastest eluding isomer, as a clear oil (2.33 g, 48%) sufficiently pure for the next step. Diastereomeric excess >95% based on 1H NMR.

Workup

  1. stirringthe solution was stirred at this temperature for 30 min
  2. customThe cooling bath was removed
  3. waitto reach room temperature overnight
  4. customThe mixture was quenched with saturated aqueous NH4Cl solution (75 mL) and EtOAc (150 mL)
  5. customThe phases were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-94808fd7e5b54a3b9c44cffbe5724a86
Source dataset
uspto-grants-2013_12
Patent number
US08598213B2

Reaction notes

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