Aluminium lithium hydride → HCID 86722363, compound

A suspension of LAH (38.0 mg, 1.00 mmol) in ether (1 mL) was stirred under nitrogen and cooled to 0° C. A solution of (3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (33, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rx=Benzyl) (89 mg, 0.167 mmol) in THF (3 mL) was added maintaining reaction temperature under 5° C. and the mixture was allowed to stir at rt for about 54 h. The reaction was diluted with THF (2 mL) and quenched by addition of water (40 μL), then 2N NaOH (40 μL) and then water (80 μL). The reaction was stirred overnight at rt. The mixture was dried with Na2SO4 and filtered through Celite®, rinsing with THF (5 mL) and EtOAc (10 mL). The combined organics were concentrated under reduced pressure to yield crude ((3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-12b-yl)methanamine (34, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rx=Benzyl). LC/MS, method 3, Rt=2.41 min, MS m/z 538 (M+H)+. The residue was used in step #3 without further purification.

1. temperaturemaintaining
2. customreaction temperature under 5° C.
3. stirringto stir at rt for about 54 h
4. customquenched by addition of water (40 μL)
5. stirringThe reaction was stirred overnight at rt
6. dry with materialThe mixture was dried with Na2SO4
7. filtrationfiltered through Celite®
8. washrinsing with THF (5 mL) and EtOAc (10 mL)
9. concentrationThe combined organics were concentrated under reduced pressure

ORD record

ord-39c2f07b60744fb89e0a74514d1efe3d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193744B2