Formaldehyde → racemic (2'S,3S,4'R)-4'-[5-bromo-2-(1-methyl-4-piperidinyloxy)-phenyl]-6-chloro-2'-(3-fluorophenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

To a mixture of racemic (2′S,3S,4′R)-4′-[5-bromo-2-(4-piperidinyloxy)-phenyl]-6-chloro-2′-(3-fluorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (150 mg, 0.25 mmol) in methanol (10 mL) was added an aqueous solution (37 wt %, Aldrich) of formaldehyde (0.03 mL, 0.38 mmol) and NaCNBH3 (25 mg, 0.38 mmol). The reaction mixture was stirred at room temperature for 1 h, then concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (MeOH:EtOAc:triethylamine=12:88:5) to give racemic (2′S,3S,4′R)-4′-[5-bromo-2-(1-methyl-4-piperidinyloxy)-phenyl]-6-chloro-2′-(3-fluorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 100 mg, 65%).

1. concentrationconcentrated
2. customThe residue was partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with ethyl acetate
5. washwashed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by chromatography (MeOH:EtOAc:triethylamine=12:88:5)

ORDレコード

ord-dedb24bc86a24b0088a74c3692023df4

出典データセット

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07776875B2