N,N,N',N'-Tetramethylethylenediamine → 1-(hydroxymethyl)-3,4-dihydro-1H-isochromene-5-carbonitrile

HRID 2173260Notes

Reaction equation

HRID 2173260 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[CH2:12][OH:13].[CH3:14][N:15](CCN(C)C)C>CN(C=O)C.[C-]#N.[C-]#N.[Zn+2]>[OH:13][CH2:12][CH:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([C:14]#[N:15])[C:3]=2[CH2:4][CH2:5][O:6]1

Participants

5

Reactant 2

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 66646784(5-bromo-3,4-dihydro-1H-isochromen-1-yl)methanol

Product 1

HCID 666465561-(hydroxymethyl)-3,4-dihydro-1H-isochromene-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (5-bromo-3,4-dihydro-1H-isochromen-1-yl)methanol (390 mg, 1.6 mmol), Zn(CN)2 (113 mg, 0.960 mmol), TMEDA (0.37 mg), xantphose (4.6 mg) and Pd(dba)3 (2.6 mg) in anhydrous DMF was microwaved 10 min at 100° C. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried and concentrated. The residue was purified with prep-HPLC to give 1-(hydroxymethyl)-3,4-dihydro-1H-isochromene-5-carbonitrile. 1H-NMR (400 MHz, CDCl3) δ 7.49˜7.50 (m, 1H), 7.24˜7.48 (m, 2H), 4.76˜4.78 (in, 1H), 4.17˜4.22 (m, 1H), 3.76˜3.95 (m, 3H), 3.01˜3.09 (m, 1H), 2.89˜2.95 (m, 1H).

Workup

  1. customwas microwaved 10 min at 100° C
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified with prep-HPLC

Sources & evidence

ORD record
ord-8c783016016f4605b25a85fd076f68b1
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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