Water → 3-(3-Chloro-5-fluorophenyl)-1-ethylazetidin-3-ol

HRID 2041887Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:13])[CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:21][CH3:22].O>C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:13])[CH2:12][N:11]([CH2:21][CH3:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-(3-chloro-5-fluorophenyl)azetidin-3-ol (0.41 g, 2.03 mmol), potassium carbonate (0.56 g, 4.06 mmol) and iodoethane (0.31 g, 2.03 mmol) in acetonitrile (5 ml) was heated at 120° C. under microwave irradiation for 10 min. Water (50 ml) and ethyl acetate (50 ml) was added and the organic phase was collected. The aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic phase was dried (Na2SO4) and evaporated under reduced pressure to give the crude product. Purification by flash column chromatography on silica gel (ethyl acetate) gave 0.28 g (60%) of the title compound. The amine was converted to the fumaric acid salt and recrystallized from ethanol/diethyl ether/diisopropyl ether: M.p. 166-168° C. MS m/z (relative intensity, 70 eV) 229 (M+, 1), 172 (23), 130 (24), 109 (33), 58 (bp).

Workup

customthe organic phase was collected
extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
dry with materialThe combined organic phase was dried (Na2SO4)
customevaporated under reduced pressure
customto give the crude product
customPurification by flash column chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record: ord-4652aae95b8240f3b3f5d251a489b02e
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586572B2

Reaction notes

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