2-[5-(4-cyanophenyl)-1-benzofuran-2-yl]ethyl Methanesulfonate → 4-(2-{2-[(2S)-2-(fluoromethyl)-1-pyrrolidinyl]ethyl}-1-benzofuran-5-yl)benzonitrile

HRID 1064778Notes

Reaction equation

HRID 1064778 reaction equation
CS(O[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=3)=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[F:25][CH2:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1>>[F:25][CH2:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][N:28]1[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[CH:19][CH:18]=3)=[CH:13][C:11]=2[CH:12]=1

Participants

3

Reactant 2

HCID 113936782-[5-(4-cyanophenyl)-1-benzofuran-2-yl]ethyl MethanesulfonateHCID 51980281(2S)-2-(Fluoromethyl)pyrrolidine

Product 1

HCID 675340284-(2-{2-[(2S)-2-(fluoromethyl)-1-pyrrolidinyl]ethyl}-1-benzofuran-5-yl)benzonitrile

Procedure

The product from Example 1C and the product from Example 164C were processed as described in Example 1D to provide the titled compound, except that potassium carbonate was substituted for sodium carbonate, and the reaction was run at 60° C. for 3 days, then worked up by pouring into toluene. The organic phase was extracted with 7:2:1 of water/N-methylpyrrolidinone/10% aqueous methanesulfonic acid, and the aqueous phase then covered with isopropyl acetate and adjusted to pH 11 with 50% aqueous NaOH. After shaking and separation of the layers, the isopropanol extract was saved, then combined with a second isopropanol extract of the aqueous layer. The combined isopropanol extract was washed three times with 5% aqueous NaHCO3, water, dried over magnesium sulfate, filtered, and concentrated in vacuo to a brown oil. The free base was converted to the mono-L-tartrate salt by addition of 1 equivalent of L-tartaric acid to the free base in ethanol. Two hours after removal of some of the ethanol under vacuum, the mixture deposited an off-white solid. The solid was collected by filtrate and dried in vacuo overnight to give the title product as the tartrate salt of 4-{2-[2-(2(R)-fluoromethyl-pyrrolidin-1-yl)-ethyl]-benzofuran-5-yl}-benzonitrile, mp 156.3° C., MS m/z (M+H)+349; 13C NMR (DMSO) δ 158.6, 154.2, 145.2, 133.2, 132,7, 129.4, 127.7, 122.8, 119.2, 118.9, 111.2, 109.4, 103.0, 85.6 and 84.3, 72.1, 62.8, 53.5, 52.3, 27.2, 26.4, 22.7.

Sources & evidence

ORD record
ord-e5c90dd7654b4e48b11fd51318586ca5
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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