Benzaldehyde → HCID 131734188, compound

HRID 718794Notes

Reaction equation

HRID 718794 reaction equation
[Na].C(O)C.[F:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:20]3[C:15](=[CH:16][C:17]4[C@@:25]5([CH2:31][C:32]6C=CC=CN=6)[CH2:26][CH2:27][C:28](=[O:30])[CH2:29][C@H:24]5[CH2:23][CH2:22][CH2:21][C:18]=4[CH:19]=3)[CH:14]=[N:13]2)=[CH:8][CH:7]=1.FC1C=CC(N2[C:53]3[C:48](=[CH:49][C:50]4[C@]5(CC6C=CC=CN=6)CCC(=O)C[C@@H]5CCC[C:51]=4[CH:52]=3)[CH:47]=N2)=CC=1.C(=O)C1C=CC=CC=1>C1COCC1>[CH:47](=[C:27]1/[CH2:26][C:25]2([CH2:31][CH3:32])[C:17]3=[CH:16][C:15]4[CH:14]=[N:13][N:12]([C:9]5[CH:8]=[CH:7][C:6]([F:5])=[CH:11][CH:10]=5)[C:20]=4[CH:19]=[C:18]3[CH2:21][CH2:22][CH2:23][CH:24]2[CH2:29][C:28]/1=[O:30])/[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 702EthanolHCID 5360545Sodium2×HCID 131734185HCID 131734185, compound

Product 1

HCID 131734188HCID 131734188, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium (0.092 g, 4.0 mmol) was added to ethanol (20 mL) and mixed at rt until the sodium was completely consumed. A solution of rac-(4aS,12bR)-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3 (2H)-one (10, R1=4-Fluorophenyl, R2=Ethyl) (1.00 g, 2.66 mmol) in THF (10 mL) was added in one portion. Benzaldehyde (0.310 g, 2.92 mmol) was added and the reaction mixture was stirred at rt for about 3 h. The organic volatiles were removed under reduced pressure. The residue was partitioned between EtOAc (70 mL) and water (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (40 g) using a gradient of 5-18% EtOAc in heptane. The product fractions were combined and concentrated under reduced pressure to give rac-(4aS,12bR,E)-2-benzylidene-12b-ethyl-9-(4-fluorophenyl)-1,4,4a,5,6,7,9,12b-octahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3(2H)-one (53, R1=4-Fluorophenyl, R2=Ethyl) (1.00 g, 81% yield); LC/MS, method 3, Rt=3.11 min.; MS m/z: 465 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.98-7.96 (m, 1H), 7.80-7.73 (m, 2H), 7.73-7.67 (m, 2H), 7.62-7.55 (m, 3H), 7.53-7.46 (m, 2H), 7.44-7.35 (m, 2H), 6.99 (s, 1H), 3.72-3.62 (m, 1H), 3.27-3.15 (m, 1H), 3.01-2.91 (m, 1H), 2.90-2.81 (m, 1H), 2.58-2.52 (m, 1H), 2.48-2.37 (m, 1H), 2.36-2.25 (m, 1H), 2.25-2.14 (m, 1H), 2.11-1.97 (m, 1H), 1.87-1.45 (m, 4H), 0.65 (t, J=7.3 Hz, 3H).

Workup

  1. customwas completely consumed
  2. customThe organic volatiles were removed under reduced pressure
  3. customThe residue was partitioned between EtOAc (70 mL) and water (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified on silica gel (40 g)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-da8d6806927347c8bac98ad5ab7c5bf6
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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