Acetic Acid → HCID 22561311, compound

HRID 983668Notes

Reaction equation

HRID 983668 reaction equation
[Li+].[CH3:2][CH:3]([N-]C(C)C)C.[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([CH:27]=O)[C:24]3[C:19](=[CH:20][C:21]([C:25]#[N:26])=[CH:22][CH:23]=3)[CH2:18][O:17]2)=[CH:12][CH:11]=1.[C:29]([OH:32])(=[O:31])[CH3:30]>>[CH2:2]([O:31][C:29]([CH2:30][CH2:27][C:16]1([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)[C:24]2[C:19](=[CH:20][C:21]([C:25]#[N:26])=[CH:22][CH:23]=2)[CH2:18][O:17]1)=[O:32])[CH3:3]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 2724682Lithium diisopropylamideHCID 22561313HCID 22561313, compound

Product 1

HCID 22561311HCID 22561311, compoundYield 57%

Procedure

Triethyl phosphonoacetate (5.1 mL, 22.8 mmol) was added to a solution of LDA (22.8 mmol) in THE (100 mL) at −30° C. under an atmosphere of nitrogen. The mixture was stirred at this temperature for 1 h, then a solution of 1-(4-fluorophenyl)-1-formyl-1,3-dihydro-5-isobenzofurancarbonitrile (5.8 g, 21.7 mmol) in THE (50 mL) was added. The mixture was allowed to warm to room temperature during 2.5 h, then poured into ice/H20. The pH was adjusted to about 5 by addition of acetic acid and the aqueous phase was extracted with iEt2O, dried and evaporated. The crude product (8.0 g) was hydrogenated in ethanol (150 mL) using Pt/C (1.7 g, 5%) as catalyst. After 16 h, the mixture was filtered through Celite and evaporated. Silica gel chromatography (heptane, EtOAc 5:1) afforded the product as an oil (4.2g. 57%). 1H NMR (CDCl3) δ 1.20 (3H, t, J=7.0 Hz); 2.25 (2H, m); 2.50 (2H, m); 4.05 (2H, q, J=7.0 Hz); 5.15 (1H, d, J=12.7 Hz); 5.19 (1H, d, J=12.7 Hz); 7.02 (2H, t, J=9.0 Hz); 7.40 (3H, m); 7.50 (1H, s); 7.60 (1 H, d, J=8.0 Hz).

Workup

  1. additionpoured into ice/H20
  2. extractionthe aqueous phase was extracted with iEt2O
  3. customdried
  4. customevaporated
  5. waitAfter 16 h
  6. filtrationthe mixture was filtered through Celite
  7. customevaporated

Sources & evidence

ORD record
ord-aedc9be75024440c93c78c505a4e6cfc
Source dataset
uspto-grants-2005_03
Patent number
US06864379B2

Reaction notes

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