Dimethyl Sulfoxide → HCID 86662315, compound

Temperature

-78 °C

An oven dried flask containing 350 ml dry CH2Cl2 was cooled to −78° C. under argon. The oxalyl chloride (31.0 g, 20.7 mL, 244 mmol, Eq: 1.30) was added followed by the addition of DMSO (28 mL, 394 mmol, 2.1 equiv) via dropwise addition. The mixture is stirred for 10 minutes and then a solution of 2-(6-chloropyridin-3-yloxy)-2-methylpropan-1-ol (41.17 g of 92% pure material, 188 mmol, Eq: 1.00), dissolved in 60 ml CH2Cl2, was added via slow dropwise addition. The mixture is stirred for 30 minutes at −78° C. Triethylamine (105 mL, 751 mmol, 4 equiv) was added and the cooling bath was removed and the reaction mixture was allowed to stir for 1 hour with warming to ambient temperature. The reaction mixture was diluted with saturated NaHCO3 (275 mL), shaken and the organic phase collected and washed with an equal volume of brine. The aqueous phase was back-extracted with DCM (2×150 ml). The combined organics phase was dried (MgSO4), filtered and concentrated in vacuo. This resulting residue was purified by Analogix MPLC (SF40-240G column) eluting with 2% to 30% EtOAC/Hex gradient over 60 minutes to afford the desired product (37.1 g) as a light yellow oil. (M+H)+=200 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 6 H) 7.07-7.34 (m, 2 H) 8.05 (d, J=3.02 Hz, 1 H) 9.79 (s, 1 H).

1. customAn oven dried flask
2. additioncontaining 350 ml dry CH2Cl2
3. additionThe oxalyl chloride (31.0 g, 20.7 mL, 244 mmol, Eq: 1.30) was added
4. additionwas added via slow dropwise addition
5. stirringThe mixture is stirred for 30 minutes at −78° C
6. customthe cooling bath was removed
7. stirringto stir for 1 hour
8. temperaturewith warming to ambient temperature
9. additionThe reaction mixture was diluted with saturated NaHCO3 (275 mL)
10. stirringshaken
11. customthe organic phase collected
12. washwashed with an equal volume of brine
13. extractionThe aqueous phase was back-extracted with DCM (2×150 ml)
14. dry with materialThe combined organics phase was dried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThis resulting residue was purified by Analogix MPLC (SF40-240G column)
18. washeluting with 2% to 30% EtOAC/Hex gradient over 60 minutes

ORD record

ord-4bfca3a6cc7f411c856704a1996e7f01

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889682B2