Tetrahydrofuran → 4-{4-Hydroxy-1-[4-(tetrahydro-2h-pyran-2-yloxy)phenoxy]butyl}-benzonitrile

HRID 1743724Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:26]=[CH:25][C:11]([O:12][CH:13]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[CH2:14][CH:15]=[CH2:16])=[CH:10][CH:9]=1.B.CSC.C1C[O:34]CC1>CCOCC>[OH:34][CH2:16][CH2:15][CH2:14][CH:13]([C:17]1[CH:18]=[CH:19][C:20]([C:21]#[N:22])=[CH:23][CH:24]=1)[O:12][C:11]1[CH:25]=[CH:26][C:8]([O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)=[CH:9][CH:10]=1

Participants

Conditions

Temperature: -5 °C

Procedure

4-{1-[4-(Tetrahydro-2H-pyran-2-yloxy)phenoxy]-3-butenyl}benzonitrile (4.6 g, 13 mmol; from step (d) above) was dissolved in dry THF (50 mL) under argon and cooled to −5° C. Borane-methylsulfide complex (BH3×SMe2) (3.5 mL of a 2 M solution in ether) was added dropwise at 0 to 5° C. The mixture was stirred at that temperature for 1.5 h. After 4 h at rt, tlc showed that the reaction was complete. The reaction mixture was quenched with 14 mL of H2O and 5 g of NaBO3. The mixture was stirred overnight, the solvent decanted off, and the residue treated with ether and decanted. The combined organic fractions were washed with brine, dried (Na2SO4), and evaporated. The crude product was purified by chromatography on silica (iso-propanol:ethyl acetate:heptane; 5:20:70). Yield: 2.44 g (58%).

Workup

waitAfter 4 h at rt
customThe reaction mixture was quenched with 14 mL of H2O and 5 g of NaBO3
stirringThe mixture was stirred overnight
customthe solvent decanted off
additionthe residue treated with ether
customdecanted
washThe combined organic fractions were washed with brine
dry with materialdried (Na2SO4)
customevaporated
customThe crude product was purified by chromatography on silica (iso-propanol:ethyl acetate:heptane; 5:20:70)

Sources & evidence

ORD record: ord-7262b0c1886c46889a4317a2821e3766
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07012074B2

Reaction notes

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