Stannous chloride dihydrate → HCID 10679317, compound

3-Fluoro-4-methoxyaniline (1, R=H, R2=CH3, R3=F) (95 g, 0.67 mol) was added to concentrated hydrochloric acid (250 mL), the suspension was stirred at ambient temperature for 18 hours, then it was cooled to 0° C. and a solution of sodium nitrite (53.7 g, 0.78 mol) in water (200 mL) was added dropwise at 0-5° C. When the addition was complete, the resulting solution was stirred at 0° C. for 1 hour then it was added dropwise at 0-5° C. to a stirred solution of tin (11) chloride dihydrate (638.9 g, 2.83 mol) in concentrated hydrochloric acid (500 mL). The mixture was allowed to warm to ambient temperature then it was stored at 4° C. for 18 hours. The resulting precipitate was collected by filtration, washed with water (400 ml), and ether (1000 mL) and dried in vacuo. The solid hydrochloride salt was basified by addition to 10% aqueous sodium hydroxide solution (800 mL), the free base was extracted into ether (2×400 mL), and the combined extracts were dried (MgSO4) and the solvent removed in vacuo to give (3-fluoro-4methoxyphenyl)hydrazine (2, R1=H, R3=CH2, R3=F) (51.9 g, 50%) as a yellow solid, mp 46-50° C.; 1HNMR (CDCl3/250 MHz): 1.5 (s, 1H, NH—NH2), 3.85 (s, 3H, OCH3), 5.0 (s, 2H, NH—NH2), 6.44 (m, 1H, phenyl 6-H), 6.60 (dd, 1H, phenyl 5-H), 6.79 (t, 1H, phenyl 2-H).

1. temperatureit was cooled to 0° C.
2. additionWhen the addition
3. stirringthe resulting solution was stirred at 0° C. for 1 hour
4. temperatureto warm to ambient temperature
5. waitit was stored at 4° C. for 18 hours
6. filtrationThe resulting precipitate was collected by filtration
7. washwashed with water (400 ml), and ether (1000 mL)
8. customdried in vacuo
9. additionThe solid hydrochloride salt was basified by addition to 10% aqueous sodium hydroxide solution (800 mL)
10. extractionthe free base was extracted into ether (2×400 mL)
11. dry with materialthe combined extracts were dried (MgSO4)
12. customthe solvent removed in vacuo

ORD record

ord-6379048805fc4c489e5fb4198f5b4311

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08884020B2