Hydrochloric Acid → HCID 117857646, compound

HRID 1483151Notes

Reaction equation

HRID 1483151 reaction equation
C[N:2]1[CH2:15][CH2:14][C@@:13]23[C:16]4[C:22]5[CH2:23][C@@H:3]1[C@@H:4]2[CH2:5][CH2:6][C:7]1([C@@H:12]3[O:18][C:17]=4[C:19]([C:24]#[N:25])=[CH:20][CH:21]=5)[O:11][CH2:10][CH2:9][O:8]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.CC1(C)CC(=O)CC(=O)C1.CO.Cl>CN(C)C=O>[O:8]1[CH2:9][CH2:10][O:11][C:7]21[CH2:6][CH2:5][C@@H:4]1[C@@:13]34[C:16]5[C:22](=[CH:21][CH:20]=[C:19]([C:24]#[N:25])[C:17]=5[O:18][C@@H:12]23)[CH2:23][C@H:3]1[NH:2][CH2:15][CH2:14]4

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 31358DimedoneHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 117857503HCID 117857503, compound

Product 1

HCID 117857646HCID 117857646, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of (4R,4aR,7aR,12bS)-3-methyl-1,2,3,4,4a,5,6,7a-octahydrospiro[4,12-methanobenzofuro[3,2-e]isoquinoline-7,2′-[1,3]dioxolane]-9-carbonitrile (5.0 g, 17.8 mmol) in dimethylformamide (50 mL) was added diisopropyl azodicarboxylate (5.4 mL, 27.5 mmol). The reaction was heated to 55° C. for 3 hours until the starting material was consumed. To the reaction was added dimedone (5.8 g, 41.4 mmol) and methanol (1.75 mL, 54.8 mmol) and the reaction heated to 60° C. for 3 hours. The reaction was allowed to cool to room temperature and poured into 0.5 M HCl(aq) (50 mL). The aqueous phase was washed with diethyl ether: ethyl acetate (3:1). The organic phase was back extracted with 0.5 M HCl(aq) and acidic phases combined before basifying with 2M NaOH until pH9. The aqueous phase was extracted with ethyl acetate (×3). The combined organic phases were washed with water/brine (×3) before drying over MgSO4 and concentrating under reduced pressure. The residue was purified by silica chromatography (5% methanol in dichloromethane to 5% NH3/methanol in dichloromethane) to give to (4R,4aR,7aR,12bS)-1,2,3,4,4a,5,6,7a-octahydrospiro[4,12-methanobenzofuro[3,2-e]isoquinoline-7,2′-[1,3]dioxolane]-9-carbonitrile as a pale yellow solid (3.90 g, 95% pure LCMS, 81% yield); [M+H]+ 325.1.

Workup

  1. customwas consumed
  2. temperaturethe reaction heated to 60° C. for 3 hours
  3. temperatureto cool to room temperature
  4. washThe aqueous phase was washed with diethyl ether: ethyl acetate (3:1)
  5. extractionThe organic phase was back extracted with 0.5 M HCl(aq) and acidic phases
  6. extractionThe aqueous phase was extracted with ethyl acetate (×3)
  7. washThe combined organic phases were washed with water/brine (×3)
  8. dry with materialbefore drying over MgSO4
  9. concentrationconcentrating under reduced pressure
  10. customThe residue was purified by silica chromatography (5% methanol in dichloromethane to 5% NH3/methanol in dichloromethane)

Sources & evidence

ORD record
ord-ba307110666a4435a8dcd9e28aef634c
Source dataset
uspto-grants-2016_08
Patent number
US09416137B2

Reaction notes

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