Sodium hydride → (r)-1-Methyl-3-(3-nitro-6-trifluoromethylphenoxy)-pyrrolidine

HRID 8634Notes

Reaction equation

HRID 8634 reaction equation
F[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[CH3:15][N:16]1[CH2:20][CH2:19][C@@H:18]([OH:21])[CH2:17]1.[H-].[Na+]>O1CCCC1.CO.CCOC(C)=O>[CH3:15][N:16]1[CH2:20][CH2:19][C@@H:18]([O:21][C:2]2[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=2[C:11]([F:14])([F:13])[F:12])[CH2:17]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 69513321-Methyl-3-pyrrolidinol, (-)-HCID 149414112-Fluoro-4-nitro-1-(trifluoromethyl)benzene

Product 1

HCID 57437881(r)-1-Methyl-3-(3-nitro-6-trifluoromethylphenoxy)-pyrrolidineYield 46%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

A solution of 2-fluoro-4-nitrobenzotrifluoride (12.4 g, 59.3 mmol, 1.0 eq) and (R)-1-methyl-pyrrolidin-3-ol (6.0 g, 59.3 mmol, 1.0 eq) in anhydrous tetrahydrofuran (150 ml) was cooled to 0° C. then slowly treated with portions of 60% sodium hydride (4.7 g, 0.12 mol, 2 eq) over 5 min. Without removing the ice bath, the reaction was allowed to come to room temperature and stir for 48 hrs. Quenched with water (50 ml) and brine (100 ml) then extracted into diethyl ether (5×100 ml). Extracts dried over anhydrous magnesium sulfate and decolorizing charcoal for 1 hr. Filtered through Celite. The filtrate was treated with silica (35 g) then evaporated to give the crude product suspended on silica. Column chromatography on silica (1% MeOH/EtOAc→5% MeOH/EtOAc) gave the product (Rf≡0.3 in 1% MeOH/EtOAc) as an orange oil (7.85 g, 46%).

Workup

  1. customWithout removing the ice bath
  2. customto come to room temperature
  3. customQuenched with water (50 ml) and brine (100 ml)
  4. extractionthen extracted into diethyl ether (5×100 ml)
  5. dry with materialExtracts dried over anhydrous magnesium sulfate
  6. customfor 1 hr
  7. filtrationFiltered through Celite
  8. additionThe filtrate was treated with silica (35 g)
  9. customthen evaporated
  10. customto give the crude product

Sources & evidence

ORD record
ord-faf8ea38427d47c980c4409fde19d250
Source dataset
uspto-grants-2006_08
Patent number
US07091204B2

Reaction notes

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