Acetic Acid → HCID 90003425, compound

HRID 718767Notes

Reaction equation

HRID 718767 reaction equation
[CH2:1]([C@:3]12[CH2:26][CH2:25][C:20]3([O:24][CH2:23][CH2:22][O:21]3)[CH2:19][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([NH:14][C:15](=[O:17])[CH3:16])[C:11]([CH3:18])=[CH:10][C:9]=12)[CH3:2].C([O-])(=O)C.[K+].CC(O)=O.C1OCCOCCOCCOCCOCCOC1.C(OC(=O)C)(=O)C.[N:61](OCCC(C)C)=O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.O>[CH2:1]([C@:3]12[CH2:26][CH2:25][C:20]3([O:24][CH2:23][CH2:22][O:21]3)[CH2:19][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:18]=[N:61][N:14]([C:15](=[O:17])[CH3:16])[C:12]=2[CH:13]=1)[CH3:2]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 7918Acetic Anhydride2×HCID 8053Isoamyl Nitrite2×HCID 2855718-Crown-6HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 90201151HCID 90201151, compound

Product 1

HCID 90003425HCID 90003425, compoundYield 64.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
70 °C

Procedure

rac-N-((4aR,11bS)-11b-ethyl-10-methyl-1,2,4,4a,5,6,7,11b-octahydrospiro[dibenzo[a,c][7]annulene-3,2′-[1,3]dioxolan]-9-yl)acetamide (25, R2=Ethyl) (0.125 g, 0.350 mmol) in CHCl3 (8 mL) was treated with potassium acetate (0.069 g, 0.699 mmol), AcOH (0.042 g, 0.699 mmol), 18-Crown-6 (15 mg, 0.057 mmol), acetic anhydride (0.071 g, 0.699 mmol) and isopentyl nitrite (0.123 g, 1.049 mmol). The mixture was warmed to about 70° C. for about 3 h then a second portion of isopentyl nitrite (0.200 g, 1.707 mmol) and acetic anhydride (0.110 g, 1.077 mmol) were added. After about 11 h the mixture was cooled to rt and treated with sat. aq. NaHCO3 (3 mL) and water (10 mL). The mixture was extracted with DCM (30 mL) then the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 0-20% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield rac-1-((4aR,12bS)-12b-ethyl-4a,5,6,7-tetrahydro-1H-spiro[benzo[6,7]cyclohepta[1,2-f]indazole-3,2′-[1,3]dioxolan]-9(2H,4H,12bH)-yl)ethanone (26, R2=Ethyl) (0.083 g, 64%); LC/MS, method 3, Rt=2.87 min, MS m/z 369 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.37 (d, J=0.6 Hz, 1H), 8.06 (s, 1H), 7.75 (s, 1H), 3.95-3.68 (m, 4H), 3.11-3.04 (m, 1H), 2.98-2.92 (m, 1H), 2.69 (s, 3H), 2.57-2.48 (m, 1H), 2.32-1.13 (m, 12H), 0.59 (t, J=7.4 Hz, 3H).

Workup

  1. temperatureAfter about 11 h the mixture was cooled to rt
  2. extractionThe mixture was extracted with DCM (30 mL)
  3. dry with materialthe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on silica gel (12 g)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9a7ef2602fcc439c9fd7cd09cb68ac16
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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