(3,4-Difluorophenyl)acetic acid → HCID 21187692, compound

HRID 1383774Notes

Reaction equation

HRID 1383774 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].[Li+].CC([N-]C(C)C)C.[CH2:21]1[CH:23]([CH:24]([OH:27])C#N)[CH2:22]1>C1COCC1.S([O-])(O)(=O)=O.[K+]>[F:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:24]([CH:23]2[CH2:21][CH2:22]2)[OH:27])[C:10]([OH:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 69571(3,4-Difluorophenyl)acetic acidHCID 2724682Lithium diisopropylamideHCID 113893592-Cyclopropyl-2-hydroxyacetonitrile

Product 1

HCID 21187692HCID 21187692, compoundYield 34.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516920Potassium bisulfateSolvent

Procedure

A solution of 3,4-difluorophenylacetic acid (2.9 g, 16.8 mmol) in 80 mL dry THF was cooled to −78° C. and treated with LDA (2.0 M heptane/THF/ethylbenzene, 42 mmol, 21 mL) for 15 minutes. Then cyclopropylcarboxaldehyde (17 mmol, 1.27 mL, 1.19 g) was added via syringe and the reaction warmed slowly to room temperature over 1 hr. The reaction mixture was diluted with 5% aqueous potassium hydrogen sulfate (50 mL), and extracted with ethyl acetate (2×150 mL). The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The lower rf material crystallized to give 1.4 g of solid. 1H NMR (CDCl3, 300 MHz) δ 7.40-7.00 (m, 3H, Ar—H), 3.75-3.60 (br m, 1H), 3.50-3.40 (m, 1H), 0.95-0.70 (m, 1H), 0.5-0.20 (m, 4H).

Workup

  1. extractionextracted with ethyl acetate (2×150 mL)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe lower rf material crystallized

Sources & evidence

ORD record
ord-d185f62624b840aab836c53e9611ce87
Source dataset
uspto-grants-2001_07
Patent number
US06255315B1

Reaction notes

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