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

HRID 1631322Notes

Reaction equation

HRID 1631322 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-pyrrole

Reagents, catalysts & solvents 3

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

Procedure

(3-fluorophenyl)magnesium bromide (203 mL, 102 mmol, 0.5 M in ether) was slowly added via syringe to a solution of (R)-3-(tert-butyldimethylsilyloxy)-4-chlorobutanenitrile (9.50 g, 40.6 mmol) in MTBE (120 mL). The reaction was stirred for two hours and DME (35 mL) was slowly added over 15 minutes followed by EtOH (23 mL). After stirring overnight, brine (50 mL) and 1M NaOH (50 mL) were added and the reaction stirred for 1 hour. The reaction mixture was filtered through a pad of Celite and the collected solids were washed with EtOAc. The filtrate was washed with 1N NaOH and brine, filtered through phase-separator paper and concentrated to provide the title compound that was used directly in the next step. MS (apci) m/z=294.2 (M+H).

Workup

  1. stirringAfter stirring overnight
  2. stirringthe reaction stirred for 1 hour
  3. filtrationThe reaction mixture was filtered through a pad of Celite
  4. washthe collected solids were washed with EtOAc
  5. washThe filtrate was washed with 1N NaOH and brine
  6. filtrationfiltered through phase-separator paper
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-629461e618b549e1a1589c4210de9a5a
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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