Iodine → tert-Butyl 3-(2-aminoethyl)azetidine-1-carboxylate

tert-Butyl 3-(2-amino-2-oxoethyl)azetidine-1-carboxylate (70 mg, 0.327 mmol) was dissolved in THF (2 mL) and cooled on an ice-bath. Borane dimethyl sulfide complex (0.41 mL, 2M in THF) was added dropwise, whereafter the mixture was refluxed for 6 h. The reaction mixture was allowed to attain rt and a mixture of DIPEA:MeOH (0.6 mL, 1:2) and iodine (166 mg, 0.654 mmol) was added. The mixture was stirred at rt overnight and then evaporated to dryness. Water (5 mL) and EtOAc (5 mL) were added to the residue an the two phases were separated. Saturated, aqueous NaHCO3 (1 mL) was added into the water phase, and it was extracted with EtOAc (5 mL×4). NaOH (1M, ca 1 mL) was added into the water phase and it was extracted with EtOAc (5 mL×2). The extracts were combined, dried (Na2SO4) and evaporated, and the residue was purified by using an ion exchange column (ISOLUTE PRS, 2 g/15 mL), eluting with MeOH and DCM (10:90), then MeOH and then MeOH (saturated with NH3) to give the title compound (35 mg, 53.5%). 1H NMR (400 MHz, CDCl3): 1.41 (s, 9H), 1.71 (dt, 2H), 2.49-2.60 (m, 1H), 2.64 (t, 2H), 3.54 (dd, 2H), 3.99 (t, 2H); 13C NMR (100 MHz, CDCl3): 26.6, 28.3, 38.3, 39.8, 54.3 (br), 79.1, 156.3.

1. temperaturecooled on an ice-bath
2. temperaturewas refluxed for 6 h
3. customto attain rt
4. customevaporated to dryness
5. additionWater (5 mL) and EtOAc (5 mL) were added to the residue an the two phases
6. customwere separated
7. additionSaturated, aqueous NaHCO3 (1 mL) was added into the water phase, and it
8. extractionwas extracted with EtOAc (5 mL×4)
9. additionNaOH (1M, ca 1 mL) was added into the water phase and it
10. extractionwas extracted with EtOAc (5 mL×2)
11. dry with materialdried (Na2SO4)
12. customevaporated
13. customthe residue was purified
14. washeluting with MeOH and DCM (10:90)

ORD record

ord-12eb21dc798a4d338d0ea30a957a7cc6

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723333B2