3-{2-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-ethoxy}-4-fluoro-benzonitrile → 3-{(S)-2-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile

HRID 708611Notes

Reaction equation

HRID 708611 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][O:6][C:7]1[CH:8]=[C:9]([C:13](=[O:25])[CH2:14][O:15][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[F:24])[C:19]#[N:20])[CH:10]=[CH:11][CH:12]=1>C1(C)C=CC=CC=1.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][O:6][C:7]1[CH:8]=[C:9]([C@H:13]([OH:25])[CH2:14][O:15][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[F:24])[C:19]#[N:20])[CH:10]=[CH:11][CH:12]=1

Participants

4

Reactant 1

HCID 583271093-{2-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-ethoxy}-4-fluoro-benzonitrile

Product 1

HCID 583271373-{(S)-2-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(S)-CBS reagent (46.5 mL, 1M in toluene) was added to a THF solution (200 mL) of borane-diethylaniline complex (15.16 g) were stirred together 15 min at room temperature. 3-{2-[3-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-ethoxy}-4-fluoro-benzonitrile (20 g) in 600 mL of dry THF was then added through an addition funnel at rt over 20 minutes. The mixture was stirred for 15 minutes and then was quenched by slow addition of 60 mL MeOH. After gas evolution ceased, the mixture was evaporated and water was added to the residue and extracted with ethyl acetate. Ethyl acetate layer separated and washed with water, brine, dried (Na2SO4), filtered, and evaporated. The residue was purified by silicagel column (DCM; 10% EtOAc in DCM) to get pure product. 1H NMR (400 MHz, CDCl3): 7.55 (d, 1H), 7.45 (d, 1H), 7.15-7.35 (m, 4H), 7.09 (t, 1H), 7.04 (d, 1H), 6.92 (m, 1H), 5.15 (m, 1H), 5.04 (s, 2H), 4.10 (m, 2H), 2.63 (d, 1H).

Workup

  1. stirringThe mixture was stirred for 15 minutes
  2. customwas quenched by slow addition of 60 mL MeOH
  3. customthe mixture was evaporated
  4. additionwater was added to the residue
  5. extractionextracted with ethyl acetate
  6. customEthyl acetate layer separated
  7. washwashed with water, brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by silicagel column (DCM; 10% EtOAc in DCM)
  12. customto get pure product

Sources & evidence

ORD record
ord-1772ade2309e47d1887b8a93531b71a4
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

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