3-(2-(4-((3,4-Dichlorobenzyl)oxy)phenyl)-2-oxoethoxy)-4-fluorobenzonitrile → 3-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile

HRID 391836Notes

Reaction equation

HRID 391836 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:12]=[CH:11][C:10]([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:9][CH:8]=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:12]=[CH:11][C:10]([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:9][CH:8]=1

Participants

4

Reactant 1

HCID 583271623-(2-(4-((3,4-Dichlorobenzyl)oxy)phenyl)-2-oxoethoxy)-4-fluorobenzonitrile

Product 1

HCID 583270913-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-hydroxy-ethoxy}-4-fluoro-benzonitrile

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

100 mL dry THF, 75 mL of 1M (R)-CBS reagent in toluene, and 26.7 mL borane-diethylaniline complex were stirred together 20 min at room temperature. 3-{2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-ethoxy}-4-fluoro-benzonitrile (31.7 g) in 700 mL dry THF was then added through an addition funnel at rt over 30 minutes. The mixture stirred for 30 min, then was quenched by slow addition of 100 mL MeOH. After gas evolution ceased the mixture was evaporated to a yellow oil. The oil was dissolved in 200 mL ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate and concentrated. The residue was stirred with hexanes and the hexanes layer removed. The resulting residue was purified over silica gel (DCM). 1H NMR (400 MHz, CDCl3): 7.54 (d, 1H), 7.46 (d, 1H), 7.38 (m, 2H), 7.3-7.15 (m, 4H), 6.97 (m, 2H), 5.13 (m, 1H), 5.03 (s, 2H), 4.10 (m, 2H), 2.64 (d, 1H).

Workup

  1. customwas quenched by slow addition of 100 mL MeOH
  2. customwas evaporated to a yellow oil
  3. dissolutionThe oil was dissolved in 200 mL ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. stirringThe residue was stirred with hexanes
  8. customthe hexanes layer removed
  9. customThe resulting residue was purified over silica gel (DCM)

Sources & evidence

ORD record
ord-ff35da10c5de42e48b3e1b7537dff134
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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