2-(Diisopropylamino)ethyl chloride → 3-oxo-1-phenyl-Cyclobutanecarboxylic acid

HRID 1955279Notes

Reaction equation

HRID 1955279 reaction equation
[C:1]1([C:7]2([C:15]([OH:17])=[O:16])[CH2:10][C:9](OC)([O:11]C)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CCCl)C(C)C)(C)C>CC(O)=O>[C:1]1([C:7]2([C:15]([OH:17])=[O:16])[CH2:8][C:9](=[O:11])[CH2:10]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 73122-(Diisopropylamino)ethyl chlorideHCID 23294958HCID 23294958, compound

Product 1

HCID 232949423-oxo-1-phenyl-Cyclobutanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

1-Phenyl-3-oxocyclobutanecarboxylic acid was prepared by refluxing 1-phenyl-3,3-dimethoxycyclobutanecarboxylic acid (8.5 mmol) with 90% HOAc, evaporating the reaction mixture, taking up the residue in 0.1 M HCl and Et2O, extracting the aqueous layer with Et2O and drying (Na2SO4) and evaporating the organic layer. The crude oxocarboxylic acid was dissolved in DMF (30 mL) and then added to NaH (60% dispersion in mineral oil, 20 mmol, washed twice with hexane) at ambient temperature. After 30 min N,N-diisopropyl-2-chloroethylamine (1.8 mmol) was added. After 2 h, the reaction mixture was partitioned between H2O and toluene. The crude product was chromatographed on silica gel using toluene-Et3N 98:2 as eluent. The afforded oil was dissolved in Et2O and HCl (g)/Et2O was added whereby the product crystallized to yield 0.25 g (10%); mp 133-135° C.; 1H NMR (CDCl3) δ 1.39 (d,12H), 3.10 (m, 2H), 3.54 (m, 4H), 4.05 (m, 2H), 4.72 (t, 2H), 7.38 (m, 5H), 11.8 (br, 1H). Anal. (C19H27NO3.HCl) C, H, N.

Workup

  1. customevaporating the reaction mixture
  2. extractionEt2O, extracting the aqueous layer with Et2O
  3. dry with materialdrying (Na2SO4)
  4. customevaporating the organic layer
  5. dissolutionThe crude oxocarboxylic acid was dissolved in DMF (30 mL)
  6. additionadded to NaH (60% dispersion in mineral oil, 20 mmol
  7. washwashed twice with hexane) at ambient temperature
  8. customthe reaction mixture was partitioned between H2O and toluene
  9. customThe crude product was chromatographed on silica gel
  10. dissolutionThe afforded oil was dissolved in Et2O
  11. additionHCl (g)/Et2O was added whereby the product
  12. customcrystallized
  13. customto yield 0.25 g (10%)

Sources & evidence

ORD record
ord-055be09d7797414eb9bce8bb2298fba0
Source dataset
uspto-grants-2000_09
Patent number
US06124354

Reaction notes

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