N,N,N',N'-Tetramethylethylenediamine → 3-Ethyl-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]benzonitrile

HRID 1023412Notes

Reaction equation

Br[C:2]1[CH:15]=[CH:14][C:5]([CH2:6][O:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)=[C:4]([CH2:16][CH3:17])[CH:3]=1.[C-]#N.[Na+].[CH3:21][N:22](CCN(C)C)C>C1(C)C=C(C)C=C(C)C=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:16]([C:4]1[CH:3]=[C:2]([CH:15]=[CH:14][C:5]=1[CH2:6][O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1)[C:21]#[N:22])[CH3:17]

Participants

Conditions

Temperature: 170 °C

Procedure

A solution of Intermediate 1 (2.9 g, 9.7 mmol), sodium cyanide (950 mg, 19.4 mmol), palladium (II) acetate (109 mg, 0.49 mmol), TMEDA (2.2 mL, 14.9 mmol), and 1,5-dis(diphenylphosphino)pentane (855 mg, 1.94 mmol) in mesitylene (50 mL) was bubbled with argon for 10 min. The degassed reaction mixture was heated to 170° C. for 16 h. After cooling to RT, the reaction mixture was diluted with water, stirred for another 10 min then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. Purification by MPLC (40% ethyl acetate in hexanes) gave rise to 2.23 g of Intermediate 4 as colorless oil.

Workup

customThe degassed reaction mixture
temperatureAfter cooling to RT
extractionthen extracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customPurification by MPLC (40% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-4bcdd8a646a74603ac1b6becec13f96f
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722712B2

Reaction notes

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