Iodoethane → 3-(3-Chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-ol

HRID 1931821Notes

Reaction equation

HRID 1931821 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([Cl:21])[CH:15]=2)([OH:13])[CH2:9]1)[C:2]1C=CC=CC=1.ICC>>[Cl:21][C:16]1[CH:15]=[C:14]([C:10]2([OH:13])[CH2:11][CH2:12][N:8]([CH2:1][CH3:2])[CH2:9]2)[CH:19]=[C:18]([F:20])[CH:17]=1

Participants

3

Reactant 2

HCID 6340IodoethaneHCID 685158581-Benzyl-3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol

Product 1

HCID 251457773-(3-Chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-olYield 49.4%

Conditions

Temperature
120 °C

Procedure

A mixture of (−)-1-benzyl-3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol (0.66 g, 2.16 mmol) and iodoethane (4 mL, 50.2 mmol) was refluxed for 4 h. The mixture was evaporated and tert-butyl methyl ether (20 mL) was added. The solvent was decantated off, morpholine (5 mL) was added and the mixture was heated under microwave irradiation at 120° C. for 30 minutes. The mixture was evaporated and purified twice by flash chromatography on silica gel (methanol/ethyl acetate, 7:3 to 3:7 and isocratic 1:1) to give the title compound (0.26 g). [α]D=−21.4° (methanol). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether/diisopropyl ether: M.p. 117-118° C.; MS m/z (relative intensity, 70 eV) 243 (M+, 23), 157, (78), 130 (82), 129 (95), 71 (bp).

Workup

  1. temperaturewas refluxed for 4 h
  2. customThe mixture was evaporated
  3. additiontert-butyl methyl ether (20 mL) was added
  4. additionmorpholine (5 mL) was added
  5. customThe mixture was evaporated
  6. custompurified twice by flash chromatography on silica gel (methanol/ethyl acetate, 7:3 to 3:7 and isocratic 1:1)

Sources & evidence

ORD record
ord-084a836073e7484aa36e26b12992edf7
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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