Water → 2-Bromo-5-(1,3-dioxan-2-yl)pyridine

To a solution of 6-bromopyridine-3-carbaldehyde (25 g, 134 mmol) in toluene (130 mL) were added 1,3-propanediol (20.45 g, 269 mmol) and 10-camphorsulfonic acid (3.12 g, 13.44 mmol). The reaction mixture was heated to reflux, with azeotropic removal of the evolved water, for 50 minutes, cooled down to r.t. and concentrated. The residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 solution (100 mL). Organic phase was collected and the aqueous phase was extracted with EtOAc (2×150 mL). Combined organic fractions were washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to yield a brown solid which was triturated with Et2O and hexane (10/200 mL), to afford intermediate 316 (27.7 g, 84% yield) as a beige solid. MS (m/z): 244.1, 246.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.40 (d, J=2.4 Hz, 1H), 7.35 (dd, J=8.0, 2.4 Hz, 1H), 7.66 (dd, J=8.0, 0.4 Hz, 1H), 5.61 (s, 1H), 4.15 (ddd, J=11.8, 5.0, 1.2 Hz, 2H), 3.98-3.91 (m, 2H), 2.028-1.95 (m, 1H), 1.46 (d quint, J=13.2, 1.2 Hz, 1H).

1. temperatureThe reaction mixture was heated
2. concentrationconcentrated
3. customThe residue was partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 solution (100 mL)
4. customOrganic phase was collected
5. extractionthe aqueous phase was extracted with EtOAc (2×150 mL)
6. washCombined organic fractions were washed with brine (100 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield a brown solid which
11. customwas triturated with Et2O and hexane (10/200 mL)

ORDレコード

ord-b8de08bb810e431bbc35bc65d00f7521

出典データセット

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08729268B2