Pyridine → Citalopram

HRID 858918Notes

Reaction equation

[I-].[K+].[Cu][C:4]#[N:5].[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[C:21]3[C:16](=[CH:17][C:18](Br)=[CH:19][CH:20]=3)[CH2:15][O:14]2)=[CH:9][CH:8]=1.[C:23]1([CH3:29])C=CC=C[CH:24]=1.[N:30]1[CH:35]=CC=C[CH:31]=1>N>[CH3:31][N:30]([CH3:35])[CH2:24][CH2:23][CH2:29][C:13]1([C:10]2[CH:11]=[CH:12][C:7]([F:6])=[CH:8][CH:9]=2)[C:21]2[C:16](=[CH:17][C:18]([C:4]#[N:5])=[CH:19][CH:20]=2)[CH2:15][O:14]1

Participants

Conditions

Temperature: 100 °C

Procedure

Potassium iodide (10 g), Copper (I) cyanide (48.5 g) were added to a solution of the [1-(3-dimethylamino)propyl)]-1-(4-fluorophenyl)-1,3-dihydro-5-bromoisobenzofuran (10 g) in pyridine (10 ml). The reaction mixture was heated to 135–145° C. and maintained for 28 hours. The reaction mixture was cooled to 100° C. and poured in ammonia solution containing toluene stirred for 2 hours to get a clear separation of layers. Then the organic layer after acid base treatment was separated and washed with water twice (2×300 ml) and dried with anhydrous sodium sulfate. The toluene layer was distilled to get the crude 1-[3-(dimethylamino) propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile base 74 gm with the following HPLC profile.

Workup

temperatureThe reaction mixture was heated to 135–145° C.
temperaturemaintained for 28 hours
customto get
customa clear separation of layers
customThen the organic layer after acid base treatment was separated
washwashed with water twice (2×300 ml)
dry with materialdried with anhydrous sodium sulfate
distillationThe toluene layer was distilled

Sources & evidence

ORD record: ord-a2e2f6dfe2ea43adaefa2936ec44a2c7
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07148364B2

Reaction notes

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