Sodium borohydride → HCID 57956104、化合物

温度

0 °C

A mixture of 5-chloro-2-(3-methoxy-propyl)-pyridine-4-carbaldehyde (21.0 g, 98.2 mmol) and cyclopropylamine (13.8 mL, 196 mmol) in MeOH (450 mL) was stirred at rt overnight. NaBH4 (4.83 g, 128 mmol) was added at 0° C., and the mixture was stirred at rt overnight. Ice was added, and the mixture was concentrated under reduced pressure. The crude product was dissolved in EtOAc, and this mixture was washed with aq. 1M NaOH. The aq. layer was extracted back with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:5→1:4→1:3→1:1→3:1→EtOAc) yielded the title compound (11.8 g) and [5-chloro-2-(3-methoxy-propyl)-pyridin-4-ylmethylene]-cyclopropyl-amine (10.7 g). This unreacted imine was dissolved in MeOH (20 mL), and this sol. was cooled to 0° C. NaBH4 (3.20 g, 84.6 mmol) was added, and the mixture was stirred at rt overnight. NaBH4 (3.20 g, 84.6 mmol) was added again, and the mixture was stirred for 3 days. Ice was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The crude product was dissolved in EtOAc and the resulting mixture was washed with aq. 1M NaOH. The aq. phase was extracted back with EtOAc. The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:3→1:2→1:1→EtOAc) yielded the title compound (9.40 g). The fractions of the title compounds were mixed together (21.2 g, 85%). LC-MS: tR=0.55 min; ES+: 296.16.

1. stirringthe mixture was stirred for 3 days
2. additionIce was added to the reaction mixture
3. concentrationthe mixture was concentrated under reduced pressure
4. dissolutionThe crude product was dissolved in EtOAc
5. washthe resulting mixture was washed with aq. 1M NaOH
6. extractionThe aq. phase was extracted back with EtOAc
7. dry with materialextracts were dried over MgSO4
8. filtrationfiltered
9. customthe solvents were removed under reduced pressure
10. customPurification of the crude by FC (EtOAc/heptane 1:3→1:2→1:1→EtOAc)

ORDレコード

ord-041aeb311da847d991063a8b21f755e6

出典データセット

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07968720B2