Malononitrile → HCID 86678956, compound

HRID 2203304Notes

Reaction equation

HRID 2203304 reaction equation
[C:1](#[N:5])[CH2:2][C:3]#[N:4].CC(C)([O-])C.[K+].Br[C:13]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([CH3:18])[C:14]([O:16][CH3:17])=[O:15].C(=O)=O.CO>C1COCC1>[C:3]([CH:2]([C:1]#[N:5])[C:13]([CH3:18])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:14]([O:16][CH3:17])=[O:15])#[N:4]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 10857674HCID 10857674, compoundHCID 21973728Carbon dioxide methanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 86678956HCID 86678956, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Malononitrile (4.29 g, 65 mmol) and potassium t-butoxide (7.29 g, 65 mmol) were added to a THF (100 mL) solution containing the intermediate from Step B (15.8 g, 65 mmol). The reaction solution was then placed in an 85° C. oil bath for 4 hours. The solution was then cooled to room temperature and partitioned between saturated aqueous ammonium chloride and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude was purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated racemic product. 1H NMR (500 MHz, CHCl3-d): δ 7.44-7.42 (m, 3H); 7.38-7.36 (m, 2H); 4.50 (s, 1H); 3.80 (s, 3H); 2.00 (s 3H). The racemic material was resolved on a Berger SFC II preparative instrument using a ChiralPak AD-H, 250×30 mm I.D. column and a SFC CO2/Methanol eluent.

Workup

  1. customwas then placed in an 85° C.
  2. customfor 4 hours
  3. custompartitioned between saturated aqueous ammonium chloride and ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by silica gel chromatography
  9. customto give the indicated racemic product

Sources & evidence

ORD record
ord-38b923a92a3946a09b27d67c9aa9178b
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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