Iodoethane → 3-(3-Chloro-2-fluorophenyl)-1-ethylpyrrolidin-3-ol

HRID 1931824Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

In a sealed tube a mixture of (+)-1-benzyl-3-(3-chloro-2-fluorophenyl)pyrrolidin-3-ol (0.31 g, 1.01 mmol), dimethyl formamide (3 mL) and iodoethane (0.16 mL, 2.02 mmol) was heated under microwave irradiation at 80° C. for 2×15 minutes. The resulting mixture was evaporated, morpholine (2 mL) was added and the mixture was heated under microwave irradiation at 130° C. for 30 minutes. Aqueous LiCl (5%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (2×50 mL, dried (Na2SO4) and evaporated. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1) gave the title compound (0.131 g). [α]D=+27.2° (methanol). The amine was converted to the oxalic acid salt and recrystallized from methanol/diethyl ether/diisopropyl ether: M.p. 71-74° C.; MS m/z (relative intensity, 70 eV) 243 (M+, 13), 228, (10), 157 (12), 72 (26), 71 (bp).

Workup

customThe resulting mixture was evaporated
additionmorpholine (2 mL) was added
temperaturethe mixture was heated under microwave irradiation at 130° C. for 30 minutes
additionAqueous LiCl (5%, 50 mL) was added
extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL
dry with materialdried (Na2SO4)
customevaporated
customPurification by flash chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1)

Sources & evidence

ORD record: ord-0e167ac8dc164994929fbf3e11ab8bc4
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188301B2

Reaction notes

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