Hydrochloric Acid → HCID 68829175, compound

Temperature

40 °C

Sodium hydride (60% in oil) (2.52 g, 63 mmol) was suspended in dry dimethylsulfoxide (30 mL) and 4-chlorobenzyl alcohol (12 g, 84 mmol) in dry dimethylsulfoxide (30 mL) was added over 15 min by syringe keeping the temperature below 30° C. (internal). This solution was stirred for 15 minutes to give a grey clear solution. The fluorosulfone D5 (15 g) was then added as a solid portionwise over 10 minutes keeping the temperature below 35° C. and the solution was stirred until the temperature began to fall, (approximately 10 minutes). The solution was then heated to 40° C. and stirred at this temperature for 1.5 hours with monitoring by LC and MS. The reaction mixture was then poured into 2M HCl (600 mL) and extracted with ethyl acetate (400 mL×1 and 250 mL×2) [this extraction was done by decantation into a separating funnel as leaving the oil which had precipitated in the conical flask along with some aqueous]. The ethyl acetate extracts were washed with a mixture of water 200 mL, brine 20 mL and 2M HCl 10 mL. The combined aqueous layers were cooled and basified with 12.5M sodium hydroxide and extracted with ethyl acetate (400 mL×1 and 250 mL×2), washed with brine and dried over sodium sulfate. The solvent was removed to give the title compound E31 (free base) as a cream coloured solid (18.24 g). A combined batch of 35.6 g of the free base was recrystallised from ethanol (following the addition of ethereal hydrogen chloride) which afforded the title compound E31 as the hydrochloride salt 30.6 g. MH+ 471. 1H NMR δ(DMSO) 2.78 (3H, s), 2.9-3.2 (4H, m), 3.2-3.6 (4H, m), 3.73 (3H, s), 5.19 (2H, s), 7.08 (1H, s), 7.18 (2H, d), 7.47 (4H, s), 7.79-7.83 (3H, m).

1. customthe temperature below 30° C. (internal)
2. customto give a grey clear solution
3. customthe temperature below 35° C.
4. stirringthe solution was stirred until the temperature
5. custom(approximately 10 minutes)
6. stirringstirred at this temperature for 1.5 hours with monitoring by LC and MS
7. extractionextracted with ethyl acetate (400 mL×1 and 250 mL×2) [
8. extractionthis extraction
9. customwas done by decantation into a separating funnel
10. customas leaving the oil which
11. customhad precipitated in the conical flask along with some aqueous]
12. washThe ethyl acetate extracts were washed with a mixture of water 200 mL, brine 20 mL and 2M HCl 10 mL
13. temperatureThe combined aqueous layers were cooled
14. extractionextracted with ethyl acetate (400 mL×1 and 250 mL×2)
15. washwashed with brine
16. dry with materialdried over sodium sulfate
17. customThe solvent was removed

ORD record

ord-d4710f0d5c0440caa1a445c8db455730

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07504392B2