Dimethylformamide → HCID 9924112, compound

HRID 2087100Notes

Reaction equation

HRID 2087100 reaction equation
[CH2:1]([C@:8]12[C:21]3[C:16](=[CH:17][C:18](Br)=[CH:19][CH:20]=3)[CH2:15][CH:14]=[C:13]1[CH:12]=[C:11]([O:23][CH2:24][CH3:25])[CH2:10][CH2:9]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][N:27](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[CH2:1]([C@@:8]12[CH2:9][CH2:10][C:11]([O:23][CH2:24][CH3:25])=[CH:12][C:13]1=[CH:14][CH2:15][C:16]1[CH:17]=[C:18]([C:26]#[N:27])[CH:19]=[CH:20][C:21]2=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6228Dimethylformamide2×HCID 10222296HCID 10222296, compound

Product 1

HCID 9924112HCID 9924112, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

Zinc cyanide (13.4 g, 114 mmol) was added to a solution of 4a(S)-Benzyl-7-bromo-2-ethoxy-3,4,4a,9-tetrahydro-phenanthrene (30 grams, 75.9 mmol) in DMF (200 mL) followed by tetrakis(triphenylphosphine)palladium(0), (10.5 g, 9.11 mmol) in a flask outfitted with a bleach scrubbing system. Additional dimethyl formamide (400 mL) was used to wash the sides of the flask and funnel. The suspension was heated to 80° C. After 7 hours HPLC showed no starting material and the reaction was cooled to room temperature. The suspension was diluted with EtOAc (300 mL) and filtered through a pad of Celite. The filtrate was washed with 2N NH4OH (2 times 500 mL), brine (500 mL) and water (500 mL). Upon addition of water solids began to precipitate out so additional EtOAc (200 mL) was added. The organic layer was concentrated to ½ volume and diluted with ethanol (250 mL) and water (250 mL). The resulting solids were allowed to granulate for 1 hour and then filtered. The mother liquor was concentrated slightly and a second crop was collected. After the combined crops air dried overnight a white solid was collected: 24.9 grams (72.9 mmol), 96% yield; mp 164-165° C., IR (film) ν 2227, 1657, 1631 cm−1; [α]25D+160.06; 1H NMR (acetone-d6) δ 7.62-7.56 (m, 2H), 7.29 (s, 1H), 7.09-7.06 (m, 1H), 7.01-6.95 (m, 2H), 6.51 (d, 2H, J=7.1 Hz), 5.54 (dd, 1H, J=5.4, 2.0 Hz), 5.49 (d, 1, J=1.6 Hz), 3.91 (q, 2, J=7.1 Hz), 3.07 (d, 1, J=12.5 Hz), 2.99 (dd, 1, J=21.6, 5.8 Hz), 2.81-2.72 (m, 1H), 2.73 (d, 1H, J=12.5 Hz), 2.65 (dd, 1H, J=13.7, 6.6 Hz), 2.29 (dd, 1H, J=17.8, 5.4 Hz), 2.15 (d, 1H, J=21.6 Hz), 1.83 (ddd, 1H, J=12.8, 12.8, 6.2 Hz), 1.33 (t, 3H, J=7.1 Hz); 13C NMR (acetone-d6) δ 155.3, 147.4, 138.9, 137.4, 136.0, 131.0, 130.7, 129.5, 127.2, 127.0, 126.2, 119.0, 118.4, 109.5, 98.8, 62.5, 44.2, 42.5, 32.1, 29.9, 25.5, 14.3. Anal. Calcd for C24H23NO: C, 84.42; H, 6.79; N, 4.10. Found: C, 83.82; H, 6.87; N, 4.04. The structure and absolute configuration were confirmed by single crystal X-ray analysis.

Workup

  1. washto wash the sides of the flask and funnel
  2. temperatureno starting material and the reaction was cooled to room temperature
  3. additionThe suspension was diluted with EtOAc (300 mL)
  4. filtrationfiltered through a pad of Celite
  5. washThe filtrate was washed with 2N NH4OH (2 times 500 mL), brine (500 mL) and water (500 mL)
  6. additionUpon addition of water solids
  7. customto precipitate out so additional EtOAc (200 mL)
  8. additionwas added
  9. concentrationThe organic layer was concentrated
  10. additiondiluted with ethanol (250 mL) and water (250 mL)
  11. waitto granulate for 1 hour
  12. filtrationfiltered
  13. concentrationThe mother liquor was concentrated slightly
  14. customa second crop was collected
  15. customAfter the combined crops air dried overnight a white solid
  16. customwas collected

Sources & evidence

ORD record
ord-3f2cd1d51842483393f41352456f569e
Source dataset
uspto-grants-2004_04
Patent number
US06727392B2

Reaction notes

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