Trifluoroacetic acid → 3-(3,5-Difluorophenyl)-3-methoxypyrrolidine

HRID 1188185Notes

Reaction equation

HRID 1188185 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C:10]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)([O:13][CH3:14])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[Cl-].[NH4+]>C(Cl)Cl>[F:22][C:17]1[CH:16]=[C:15]([C:10]2([O:13][CH3:14])[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:20]=[C:19]([F:21])[CH:18]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 67404226HCID 67404226, compound

Product 1

HCID 199358743-(3,5-Difluorophenyl)-3-methoxypyrrolidineYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl-3-(3,5-difluorophenyl)-3-methoxypyrrolidin-1-carboxylate (2.64 g, 8.4 mmol) in methylene chloride (20 mL), was added trifluoroacetic acid (5 mL). The mixture was stirred for 1 h at ambient temperature after which aqueous saturated ammonium chloride solution (50 ml) was added and the aqueous phase was extracted with methylene chloride (2×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated to give the crude product, purification on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) gave the title compound (1.3 g, 73%). MS m/z (rel. intensity, 70 eV) 213 (M+, 0.5), 183 (bp), 171 (89), 141 (80), 113 (88).

Workup

  1. additionwas added
  2. extractionthe aqueous phase was extracted with methylene chloride (2×50 mL)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give
  7. customthe crude product, purification
  8. washon a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1)

Sources & evidence

ORD record
ord-845acce895a34f279988798d3bf266e2
Source dataset
uspto-grants-2014_03
Patent number
US08673962B2

Reaction notes

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