1,2-Dimethoxyethane → (R)-3-(tert-butyldimethylsilyloxy)-5-(3-fluorophenyl)-3,4-dihydro-2H-pyrrole

HRID 63984Notes

Reaction equation

HRID 63984 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][CH:7]=1.[Si:10]([O:17][C@@H:18]([CH2:22]Cl)[CH2:19][C:20]#[N:21])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].COCCOC.[OH-].[Na+]>CC(OC)(C)C.[Cl-].[Na+].O.CCO>[Si:10]([O:17][C@@H:18]1[CH2:19][C:20]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:21][CH2:22]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 14798Sodium HydroxideHCID 11299266(R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanenitrileHCID 178505773HCID 178505773, compound

Product 1

HCID 66847764(R)-3-(tert-butyldimethylsilyloxy)-5-(3-fluorophenyl)-3,4-dihydro-2H-pyrroleYield 107%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 15413tert-Butyl methyl etherSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(3-Fluorophenyl)magnesium bromide (203.2 mL×0.5 M ether, 102 mmol) was slowly added (via syringe) to a solution of (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanenitrile (9.5 g, 40.6 mmol) in 120 mL of MTBE. The reaction was stirred for two hours and then DME (35 ml) was slowly added over 15 minutes, followed by EtOH (23 mL). After stirring for overnight, brine and 1 M NaOH (50 mL each) were added to the reaction. After stirring for one hour, the reaction mixture was filtered through Celite, rinsing the solid with EtOAc. The filtrate was washed with 1 N NaOH and brine, filtered through Phase Separator filter paper, and concentrated, yielding the crude product, which was carried to the next step without further purification (12.8 g, 107% yield).

Workup

  1. stirringAfter stirring for overnight
  2. stirringAfter stirring for one hour
  3. filtrationthe reaction mixture was filtered through Celite
  4. washrinsing the solid with EtOAc
  5. washThe filtrate was washed with 1 N NaOH and brine
  6. filtrationfiltered through Phase Separator
  7. filtrationfilter paper
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1c3c1036ec7e42e291be4a52c0f8d7d5
Source dataset
uspto-grants-2016_09
Patent number
US09447104B2

Reaction notes

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