Acetic Acid → HCID 54175120, compound

Temperature

0 °C

Sodium cyanoborohydride (1.15 g, 18.3 mmol) was added to a solution of benzylamine (1.04 ml, 9.5 mmol) and glacial acetic acid (2.10 ml, 36.7 mmol), in dry methanol (150 ml), at room temperature. The solution was cooled to 0° C. and a solution of the-preceding aldehyde (1.35 g, 7.3 mmol), in methanol (50 ml), was added. The mixture was warmed to room temperature and stirred for 20 h. The volatiles were removed in vacuo and the residue partitioned between EtOAc/aq. K2CO3. The aqueous was extracted with EtOAc (×3) and the combined extracts dried and evaporated. The crude product was chromatographed on silica gel eluting with CH2Cl2 /MeOH (95:5→92:8) to give the desired N-benzylaminoazetidine (1.5 g, 73%). A mixture of formic acid (99%, 18 ml) and H2O(2 ml) was added to N-tert-butyloxycarbonyl-3-(benzylamino)methyl azetidine (1.5 g, 5.3 mmol) at 0° C. The mixture was warmed to room temperature, stirred for 16 h, and the solvent then removed under vacuum. Saturated aqueous K2 CO3 (25 ml) was added to the residue and extracted with nBuOH (5×25 ml). The combined extracts were evaporated and the residue treated with CH2Cl2 (50 ml) and filtered to remove inorganics. The filtrate was dried (Na2SO4) and evaporated to give the title compound (0.512 g, 55%). δ (360 MHz, CDCl3) 2.85 (2H, s, CH2Ph), 3.36-3.39 (1H, m, CH), 3.57-3.72 (4H, m, 2 of CH2), 3.79 (2H, s, CH2), 7.23-7.34 (5H, m, Ar--H).

1. temperatureThe mixture was warmed to room temperature
2. customThe volatiles were removed in vacuo
3. customthe residue partitioned between EtOAc/aq
4. extractionThe aqueous was extracted with EtOAc (×3)
5. customthe combined extracts dried
6. customevaporated
7. customThe crude product was chromatographed on silica gel eluting with CH2Cl2 /MeOH (95:5→92:8)

ORD record

ord-20391cc30ada49a898ecef53187cc867

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05854268