Butyl bromide → HCID 25143819, compound
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH2:22][CH2:23][CH3:24].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[CH2:21]([N:11]1[CH2:12][CH2:13][C:9]([C:4]2[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=2)([OH:14])[CH2:10]1)[CH2:22][CH2:23][CH3:24]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 120 °C
Procedure
In a sealed tube a mixture of enantiomer E1 of 3-(3,5-difluorophenyl)pyrrolidin-3-ol (0.18 g, 0.92 mmol), acetonitrile (5 mL), potassium carbonate (0.25 g, 1.84 mmol) and n-butylbromide (0.1 mL, 1.01 mmol) was heated under microwave irradiation at 120° C. for 45 min. Aqueous sodium carbonate (10%, 5 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phase was dried (Na2SO4) and evaporated. Purification on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) and by flash chromatography on silica gel (ethyl acetate/methanol, 7:1) gave the title compound (0.13 g). [α]D=+21.9° (methanol). The amine was converted to the oxalic acid salt and recrystallized from methanol/diisopropyl ether: M.p. 146-147° C.; MS m/z (relative intensity, 70 eV) 255 (M+, 5), 212 (bp), 98 (66), 57 (51), 182 (39), 127 (18).
Workup
- extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
- dry with materialthe combined organic phase was dried (Na2SO4)
- customevaporated
- customPurification
- washon a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1)
Sources & evidence
- ORD record
- ord-a2e388e57c814a8fa99e43ff072b27e2
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188301B2
Reaction notes
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