Triphenylphosphine → HCID 67547481, compound

HRID 2089491Notes

Reaction equation

HRID 2089491 reaction equation
O[CH:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[CH2:5][S:4][CH2:3]1.[NH:14]1[CH:18]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:16]=[CH:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:22][O:21][C:19]([C:17]1[N:16]([CH:2]2[C:11]3[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=3)[CH2:5][S:4][CH2:3]2)[CH:15]=[N:14][CH:18]=1)=[O:20]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 67546737HCID 67546737, compoundHCID 178418785HCID 178418785, compound

Product 1

HCID 67547481HCID 67547481, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-hydroxy-isothiochroman-7-carbonitrile (630 mg, 3.3 mmol) in THF (20 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 460 mg, 3.6 mmol), and triphenylphosphine (909 mg, 3.4 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (0.66 mL, 3.4 mmol) is added. The reaction is permitted to warm to room temperature and stirred until LC-MS analysis indicates complete consumption of 4-hydroxy-isothiochroman-7-carbonitrile. The reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to provide 3-(7-cyano-isothiochroman-4-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 300.1 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 3.08-3.23 (m, 1 H), 3.32 (dd, J=14.4, 4.0 Hz, 1 H), 3.73-4.07 (m, 2 H), 3.91 (s, 3 H), 6.46-6.61 (m, 1 H), 7.15 (d, J=8.1 Hz, 1 H), 7.46 (s, 1 H), 7.49-7.54 (m, 1 H), 7.56 (s, 1 H), 7.84 (s, 1 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(7-cyano-isothiochroman-4-yl)-3H-imidazole-4-carboxylic acid methyl ester.

Workup

  1. temperatureto warm to room temperature
  2. customconsumption of 4-hydroxy-isothiochroman-7-carbonitrile
  3. additionThe reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate
  4. customThe layers are separated
  5. dry with materialthe organic layer is dried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1)

Sources & evidence

ORD record
ord-e748cd3b48df41f795c4663765d04ea2
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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