(Diethylamino)sulfur trifluoride → 1-Benzyl-3-(2,3-difluorophenyl)-3-fluoropyrrolidine

HRID 1931890Notes

Reaction equation

HRID 1931890 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])(O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(S(F)(F)[F:28])CC)C.C(=O)([O-])O.[Na+]>ClCCl>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=2[F:21])([F:28])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluoride2×HCID 516892Sodium BicarbonateHCID 685158491-Benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 685171501-Benzyl-3-(2,3-difluorophenyl)-3-fluoropyrrolidineYield 37.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol (5.3 g, 18.3 mmol) in dichloromethane (30 mL) at 0° C. was added drop wise, a solution of diethylaminosulfur trifluoride (2.93 mL, 22.4 mmol) in dichloromethane. The cooling was removed and the mixture was stirred at ambient temperature for 2 h after which an additional amount of diethylaminosulfur trifluoride (0.1 mL, 0.76 mmol) was added. The mixture was stirred for 1 h at ambient temperature after which aqueous sodium hydrogen carbonate (10%) was added and the mixture was extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (isooctane/ethyl acetate, 1:0 to 1:1) gave the title compound (2 g). MS m/z (relative intensity, 70 eV) 291 (M+, 32), 200 (18), 133 (54), 91 (bp), 65 (20).

Workup

  1. customThe cooling was removed
  2. additionwas added
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash chromatography on silica gel (isooctane/ethyl acetate, 1:0 to 1:1)

Sources & evidence

ORD record
ord-bcafeefc4a31439592de14fcf810e22c
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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