Dimethylformamide → HCID 117857503, compound

HRID 1483150Notes

Reaction equation

HRID 1483150 reaction equation
FC(F)(F)S(O[C:7]1[C:12]2[O:13][C@H:14]3[C:23]4([O:27][CH2:26][CH2:25][O:24]4)[CH2:22][CH2:21][C@@H:20]4[C@@:15]53[CH2:16][CH2:17][N:18]([CH3:29])[C@@H:19]4[CH2:28][C:10]([C:11]=25)=[CH:9][CH:8]=1)(=O)=O.[CH3:32][N:33](C)C=O>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[CH3:29][N:18]1[CH2:17][CH2:16][C@@:15]23[C:11]4[C:10]5[CH2:28][C@@H:19]1[C@@H:20]2[CH2:21][CH2:22][C:23]1([C@@H:14]3[O:13][C:12]=4[C:7]([C:32]#[N:33])=[CH:8][CH:9]=5)[O:24][CH2:25][CH2:26][O:27]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 117857432HCID 117857432, compound

Product 1

HCID 117857503HCID 117857503, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution 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]dioxolan]-9-yl trifluoromethanesulfonate (20.77 g, 45.0 mmol) in degassed dimethylformamide (400 mL) was added tetrakis(triphenylphosphine)palladium(0) (5.21 g, 4.50 mmol). After heating to 40° C., zinc cyanide (3.18 g, 27.0 mmol) was added and the reaction mixture heated at 110° C. for 6 hours. The reaction mixture was cooled to room to temperature and diluted with ethyl acetate and filtered through a pad of celite. The filtrate was diluted further with ethyl acetate and washed with water (3×500 mL). The aqueous phase was basified with sodium hydrogen carbonate solution and re-extracted with ethyl acetate and the combined organics dried (MgSO4), filtered and concentrated under reduced pressure. Purification by silica chromatography (100% dichloromethane to 5% NH3/methanol in dichloromethane) gave (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 (10.0 g, 91% pure LCMS, 63% yield over three steps); [M+H]+ 339.1.

Workup

  1. temperaturethe reaction mixture heated at 110° C. for 6 hours
  2. temperatureThe reaction mixture was cooled to room to temperature
  3. filtrationfiltered through a pad of celite
  4. additionThe filtrate was diluted further with ethyl acetate
  5. washwashed with water (3×500 mL)
  6. extractionre-extracted with ethyl acetate
  7. dry with materialthe combined organics dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by silica chromatography (100% dichloromethane to 5% NH3/methanol in dichloromethane)

Sources & evidence

ORD record
ord-e9e7701c26e542b6961f10f9e72fc314
Source dataset
uspto-grants-2016_08
Patent number
US09416137B2

Reaction notes

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