Sodium Carbonate → [4-(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-yl)phenyl]methanol

A solution (1.2 mL) of the product from Example 115A (350 mg, 1.1 mmol) in benzene (3.6 mL) was added to a mixture of palladium (II) acetate (11 mg, 0.05 mmol), and biphen-2-yl-dicyclohexylphosphine (28 mg, 0.08 mmol). The reaction mixture was then treated with 4-(hydroxymethyl)phenylboronic acid (87 mg, 0.57 mmol) in ethanol (500 μL) followed by 2M aqueous Na2CO3 (500 μL). The mixture was stirred thoroughly overnight. Additional ethanol (500 μL) was added and the mixture was stirred for four days, diluted with EtOAc, filtered, chromatographed through a short column of silica with a gradient of 0 to 2% MeOH/EtOAc, purified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size) using a gradient of 10% to 100% MeCN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min.], and then rechromatographed through a short column of silica with MeOH/CH2Cl2 to provide the title compound (12% yield). MS (ESI APCI) m/z 336 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.21 (d, 3H), 1.42-1.58 (m, 1H), 1.77-1.91 (m, 2H), 1.99-2.13 (m, 1H), 2.35-2.77 (m, 3H), 2.97-3.18 (m, 2H), 3.2-3.4 (m, 2H), 4.64 (s, 2H), 6.61 (s, 1H), 7.42 (d, 2H), 7.45-7.48 (m, 2H), 7.60 (d, 2H), 7.72 (dd, 1H).

1. stirringthe mixture was stirred for four days
2. filtrationfiltered
3. customchromatographed through a short column of silica with a gradient of 0 to 2% MeOH/EtOAc
4. custompurified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size)
5. customover 8 min
6. custom(10 min run time)
7. customthen rechromatographed through a short column of silica with MeOH/CH2Cl2

ORD record

ord-33de3ed78b4f419b841190ac9e83e9fb

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538138B2