Water → HCID 25145782, compound

HRID 1931802Notes

Reaction equation

HRID 1931802 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([F:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.O.[CH2:16](OCC)C>C(O)=O.C=O>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([F:14])[CH2:13][CH2:12][N:11]([CH3:16])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 3283Diethyl EtherHCID 25143663HCID 25143663, compound

Product 1

HCID 25145782HCID 25145782, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 712FormaldehydeSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-(3,5-difluorophenyl)-3-fluoropyrrolidine (0.17 g, 0.85 mmol) in formic acid (2.45 mL) and aqueous formaldehyde (40%, 2.2 mL) was heated at 85° C. for 1 h. Water (100 mL) and diethyl ether was added, the phases were separated and the aqueous phase was basified by the addition of aqueous sodium hydroxide (5M, 20 mL). The aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was dried (MgSO4) and evaporated. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1) gave the title compound (0.12 g). The amine was converted to the oxalic acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 128-129° C.; MS m/z (relative intensity, 70 eV) 215 (M+, bp), 194 (29), 193 (36), 151 (33), 57 (92).

Workup

  1. customthe phases were separated
  2. additionthe aqueous phase was basified by the addition of aqueous sodium hydroxide (5M, 20 mL)
  3. extractionThe aqueous phase was extracted with ethyl acetate (2×50 mL)
  4. dry with materialthe combined organic phase was dried (MgSO4)
  5. customevaporated
  6. customPurification by flash chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1)

Sources & evidence

ORD record
ord-798bfadc359e474fa2148a477a20e086
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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