Sodium Hydroxide → NEO 376

To a solution of 1,5,6,7-tetrahyro-indol-4-one (51.5 mmol) in DMSO (60 mL) was added powdered sodium hydroxide (53.9 mmol) and the mixture was stirred at ambient temperature for 0.5 h. 1-(2-Chloroethyl)-4-(3-chlorophenyl) piperazine (49.0 mmol) was then added as a solution in DMSO (20 mL) and the resulting mixture stirred at ambient temperature for 24 h then heated to approximately 60° C. for 2 h, after which time TLC (ethyl acetate:dichloromethane 1:1) showed complete reaction. The reaction was poured into ice cold water (300 mL) and stirred for 0.5 h. A solid mass formed and was separated by decanting the water. The aqueous layer was extracted with dichloromethane (100 mL). The solid mass was dissolved with dichloromethane (100 mL) and the combined organics were dried with sodium sulfate and the solvent removed under vacuum. The resulting sludge was triturated with hexanes (100 mL) for 2 h and the suspension vacuum filtered and washed with hexanes. The obtained solid was under vacuum resulting in a tan powder (14.57 g) as the titled compound, NEO-376).

1. stirringthe resulting mixture stirred at ambient temperature for 24 h
2. temperaturethen heated to approximately 60° C. for 2 h
3. customreaction
4. stirringstirred for 0.5 h
5. customA solid mass formed
6. customwas separated
7. customby decanting the water
8. extractionThe aqueous layer was extracted with dichloromethane (100 mL)
9. dissolutionThe solid mass was dissolved with dichloromethane (100 mL)
10. dry with materialthe combined organics were dried with sodium sulfate
11. customthe solvent removed under vacuum
12. customThe resulting sludge was triturated with hexanes (100 mL) for 2 h
13. filtrationthe suspension vacuum filtered
14. washwashed with hexanes

ORD record

ord-b1c43573636142768e2391af934a410b

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06770638B2