Dimethylformamide → HCID 15425895, compound

HRID 2384594Notes

Reaction equation

HRID 2384594 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[CH2:11][C@H:12]3[N:24]([CH2:25][CH:26]4[CH2:28][CH2:27]4)[CH2:23][CH2:22][C@:18]45[C:19]=2[C:20]=1[O:21][C@H:17]4[C:16](=[O:29])[CH2:15][CH2:14][C@@:13]35[OH:30])(=O)=O.[CH3:33][N:34](C=O)C>C(OCC)(=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>[CH:26]1([CH2:25][N:24]2[CH2:23][CH2:22][C@:18]34[C:19]5[C:20]6[O:21][C@H:17]3[C:16](=[O:29])[CH2:15][CH2:14][C@@:13]4([OH:30])[C@H:12]2[CH2:11][C:10]=5[CH:9]=[CH:8][C:7]=6[C:33]#[N:34])[CH2:27][CH2:28]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 15425894205375-23-1

Product 1

HCID 15425895HCID 15425895, compoundYield 61%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A mixture of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-yl trifluoromethanesulfonate [P1] (38.0 g, 80.3 mmol), zinc cyanide (18.85 g, 160.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (8.5 g, 7.36 mmol) in DMF (500 mL—degassed with argon for 3 hours) was heated at 120° C. under argon for 3 hours. The reaction mixture was allowed to return to room temperature then diluted with ethyl acetate (IL) and passed through a pad of celite. The solution was washed with water (3×1 L) and the organic phase dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave crude product that was triturated with methanol to give (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carbonitrile [P2] (17.12 g, 61% yield); LC/MS (r.t. 12.7 minutes [5 to 95% B]), 351 (M+H)+.

Workup

  1. customto return to room temperature
  2. washThe solution was washed with water (3×1 L)
  3. dry with materialthe organic phase dried (MgSO4)
  4. filtrationFiltration and removal of the solvent under reduced pressure
  5. customgave crude product that
  6. customwas triturated with methanol

Sources & evidence

ORD record
ord-1752fbe31a314ce9b3c482ef75ae024b
Source dataset
uspto-grants-2012_09
Patent number
US08263807B2

Reaction notes

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