Dimethyl methylphosphonate → Dimethyl 2-(1-butylcyclobutyl)-2-oxoethylphosphonate

HRID 28783Notes

Reaction equation

HRID 28783 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].[Li]CCCC.[CH2:13]([C:17]1([C:21](OC)=[O:22])[CH2:20][CH2:19][CH2:18]1)[CH2:14][CH2:15][CH3:16]>C1COCC1>[CH2:13]([C:17]1([C:21](=[O:22])[CH2:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4])[CH2:20][CH2:19][CH2:18]1)[CH2:14][CH2:15][CH3:16]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 69250825Methyl 1-butylcyclobutanecarboxylateHCID 178418339Butyllithium

Product 1

HCID 13389553Dimethyl 2-(1-butylcyclobutyl)-2-oxoethylphosphonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethyl methylphosphonate (1.46 g, 11.8 mmol) in anhydrous THF (25 mL) at −78° C. was added n-BuLi (7.4 mL, 1.6 M, 11.8 mmol) dropwise under Ar. The reaction was stirred for 15 minutes. A solution of methyl 1-butylcyclobutanecarboxylate (1.00 g, 5.87 mmol) in THF (5 mL) was added dropwise. The reaction mixture was stirred for 30 minutes at −78° C., after which it was allowed to warn to room temperature. The reaction was quenched with 5% HCl, extracted with CH2Cl2 (3×30 mL), the combined organic phase was washed with brine, dried (MgSO4). After concentration, flash chromatography (silica gel, 1:1 ethylacetate:hexanes), the title compound was obtained as a colorless oil. 1HNMR (CDCl3) δ 0.85˜0.89 (m, 3H), 1.05˜1.15 (m, 2H), 1.22˜1.35 (m, 2H), 1.65˜1.95 (m, 6H), 2.35˜2.50 (m, 2H), 3.00 (s, 1H0, 3.06 (s, 1H), 3.78 (s, 3H), 3.82 (s, 3H). MS (m/z) 285 (M+Na)

Workup

  1. stirringThe reaction mixture was stirred for 30 minutes at −78° C.
  2. customto warn to room temperature
  3. customThe reaction was quenched with 5% HCl
  4. extractionextracted with CH2Cl2 (3×30 mL)
  5. washthe combined organic phase was washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationAfter concentration, flash chromatography (silica gel, 1:1 ethylacetate:hexanes)

Sources & evidence

ORD record
ord-f7d944730ae2463abb0d13f3a09d3ad8
Source dataset
uspto-grants-2008_09
Patent number
US07419999B2

Reaction notes

Loading…