Hydrochloric Acid → HCID 178521031, compound

HRID 1988138Notes

Reaction equation

HRID 1988138 reaction equation
[N+](CP(=O)([O:8][CH2:9][CH3:10])OCC)#[C-].C([Li])CCC.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]2[CH2:27]C(=O)[CH2:25]2)=[CH:20][CH:19]=1.Cl>CCOCC>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[CH2:27][C@H:10]([CH:9]=[O:8])[CH2:25]2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2734699Diethyl (isocyanomethyl)phosphonateHCID 45896953-(4-Bromophenyl)cyclobutan-1-oneHCID 178418339Butyllithium

Product 1

HCID 178521031HCID 178521031, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of diethyl isocyanomethylphosphonate (0.86 mL, 5.3 mmol) in anhydrous ether (45 mL) at −78° C. under nitrogen was added n-butyl lithium (2.13 mL, 2.5 M in hexane) and the resulting mixture was stirred at −78° C. for 1 hr. Then, 3-(4-bromo-phenyl)-cyclobutanone (1 g, 4.4 mmol) in anhydrous ether (15 mL) was added dropwise over 30 minutes. The reaction mixture was allowed to warm to ambient temperature and stirred 16 hours. Concentrated hydrochloric acid (9.5 mL) was added dropwise and the reaction mixture was stirred at room temperature for 5 hrs. The mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was chromatographed on silica gel eluting with 2-3% ethyl acetate in hexanes to provide 3-(4-bromo-phenyl)-trans-cyclobutanecarbaldehyde (281 mg, 27%) as the faster eluting isomer (A1) and 3-(4-bromo-phenyl)-cis-cyclobutanecarbaldehyde (508 mg, 48%) as the slower eluting isomer (A2). A1: 1H NMR (300 MHz, CDCl3) δ 2.37 (m, 2 H), 2.72 (m, 2 H), 3.16 (m, 1 H), 3.53 (p, J=6 Hz, 1 H), 7.09 (d, J=9 Hz, 2 H), 7.44 (d, J=9Hz, 2 H), 9.95 (s, 1 H),; (DCl/NH3) m/z 239 (M+H)+; A2: 1 H NMR (300 MHz, CDCl3) δ 2.35 (m, 2 H), 2.55 (m, 2 H), 3.21 (m, 1 H), 3.52 (p, J=6 Hz, 1 H), 7.07 (d, J=9 Hz, 2 H), 7.42 (d, J=9 Hz, 2 H), 9.73 (s, 1 H); (DCl/NH3) m/z 239 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred 16 hours
  3. stirringthe reaction mixture was stirred at room temperature for 5 hrs
  4. customThe mixture was partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was chromatographed on silica gel eluting with 2-3% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8d40fa27ecbd4b65b4ec6b7a711a0edb
Source dataset
uspto-grants-2009_06
Patent number
US07553964B2

Reaction notes

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