(Aminooxy)acetic acid → HCID 59315608, compound

Temperature

50 °C

To a solution of (1R,3R,4S)-3-allyl-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (241 mmol, 50 g) in 1,3-dichloropropane (400 mL) at ambient temperature under nitrogen was added 2-bromobenzaldehyde (253 mmol, 46.9 g) followed by D/L-camphorsulphonic acid (21.55 mmol, 5 g) and the solution was heated at heated to 50° C. overnight. A further 0.05 eq of 2-bromobenzaldehyde was added and the reaction stirred at 50° C. for a further 2 hours. To the reaction mixture at 50° C. was added a methanol solution of 0.5 M hydroxylamine acetic acid (1000 mL) [solution prepared by dissolving hydoxylamine hydrochloride (46.5 g) in methanol (500 mL)] followed by addition of sodium hydroxide pellets (20 g) allowing to stir for 30 min at ambient temperature and then slowly adding glacial acetic acid (30 g) at ambient temperature stirring for a further 30 min and then diluting to 1000 mL using methanol] and left to stir at 50° C. for 3 hours. The reaction mixture was cooled to 10° C. and slowly acidified with 10M hydrochloric acid (until pH 1 was attained). This was diluted with water (250 mL) and extracted with methylene chloride (4×500 mL), the acidic aqueous was then basified to pH 14 with sodium hydroxide pellets with ice-water cooling and then extracted with methylene chloride (3×500 mL), the combined organics were dried over sodium carbonate, filtered and evaporated to give a pale green oil which was loaded onto a silica pad (400 g silica), with methylene chloride and eluted with 100% ethyl acetate to 3% methanol (containing some 2M ammonia) in ethyl acetate to give (S)-1-(2-bromophenyl)but-3-en-1-amine (18.4 g) in an enantiomeric ratio of 97.6:2.4 determined by chiral HPLC, MS (ES); m/z [M=H]+ 26 and 228. This material was converted to the hydrochloride salt with HCl in ether.

1. temperaturethe solution was heated
2. stirringto stir for 30 min at ambient temperature
3. additiondiluting to 1000 mL
4. waitleft
5. stirringto stir at 50° C. for 3 hours
6. temperatureThe reaction mixture was cooled to 10° C.
7. extractionextracted with methylene chloride (4×500 mL)
8. extractionextracted with methylene chloride (3×500 mL)
9. dry with materialthe combined organics were dried over sodium carbonate
10. filtrationfiltered
11. customevaporated
12. customto give a pale green oil which
13. washeluted with 100% ethyl acetate to 3% methanol (
14. additioncontaining some 2M ammonia) in ethyl acetate

ORD record

ord-4655c891c8cd4ce0badc0e1cdae965da

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188123B2