Acetonitrile → 3-(2-(2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-yl)benzonitrile

HRID 1064753Notes

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][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=3)=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[CH3:25][C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C([O-])([O-])=O.[Cs+].[Cs+].CC#N>C(Cl)Cl>[CH3:25][C@@H:26]1[CH2:30][CH2:29][CH2:28][N:27]1[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[C:23]#[N:24])=[CH:13][C:11]=2[CH:12]=1

Participants

Conditions

Temperature: 40 °C

Procedure

The crude product from Example 112D, the mono-(L)-tartaric acid salt of (2R)-2-methylpyrrolidine (306 mg, 1.3 mmol), and Cs2CO3 (652 mg, 2.0 mmol) were stirred in an approximately 0.2 M MeCN solution of (2R)-2-methylpyrrolidine (1.6 mL, 0.3 mmol). The mixture was heated at 40° C. overnight. More Cs2CO3 (326 mg, 1.0 mmol) and acetonitrile (0.5 mL) were added and the reaction was stirred at 40° C. for four days. The mixture was cooled to room temperature, diluted with CH2Cl2, filtered, and concentrated. The residue was chromatographed twice through a short column of silica with a 0 to 5% gradient of MeOH/CH2Cl2 to provide the title compound as an orange-tan gum (28% yield). 1HNMR (300 MHz, CD3OD) δ 1.18 (d, 3 H), 1.39-1.54 (m, 1 H), 1.75-1.87 (m, 2H), 1.96-2.09 (m, 1H), 2.27-2.39 (m, 1 H), 2.46-2.63 (m, 2 H), 2.95-3.15 (m, 2 H), 3.20-3.35 (m, 2 H), 6.63 (s, 1H), 7.49-7.52 (m, 2 H), 7.62 (dd, 1 H), 7.67 (ddd, 1 H), 7.78 (dd, 1 H), 7.90 (ddd, 1 H), 7.98 (dd, 1 H).

Workup

temperatureThe mixture was cooled to room temperature
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed twice through a short column of silica with a 0 to 5% gradient of MeOH/CH2Cl2

Sources & evidence

ORD record: ord-b5c4d524059543e691bce4b8d18f5b03
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06969730B2

Reaction notes

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