Trimethyl orthoformate → Tert-butyl 3,3-dimethoxycyclopentanecarboxylate

HRID 2217957Notes

Reaction equation

HRID 2217957 reaction equation
O=[C:2]1C[CH2:5][CH:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.CO[CH:16]([O:19][CH3:20])[O:17][CH3:18]>CC1C=CC(S(O)(=O)=O)=CC=1.O.C(Cl)Cl.CO>[CH3:20][O:19][C:16]1([O:17][CH3:18])[CH2:2][CH2:3][CH:4]([C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[CH2:5]1

Participants

5

Reactant 2

HCID 9005Trimethyl orthoformateHCID 14009986tert-Butyl 3-oxocyclopentane-1-carboxylate

Product 1

HCID 58784445Tert-butyl 3,3-dimethoxycyclopentanecarboxylateYield 90.1%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalyst2×HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of tert-butyl 3-oxocyclopentanecarboxylate (19.8 g, 107 mmol) in 1:1 DCM/methanol (150 mL) was added trimethylorthoformate (46.8 mL, 428 mmol), followed by TsOH.H2O (˜0.5 g). The reaction mixture was stirred at room temperature for 2 h. Then more TsOH.H2O (˜0.25 g) was added and the reaction mixture was stirred overnight. The reaction mixture was concentrated at room temperature and the resulting residue was dissolved in ether and washed with saturated NaHCO3 solution, then with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 15% ethyl acetate/hexane) gave 22.2 g (90%) of tert-butyl 3,3-dimethoxycyclopentanecarboxylate. 1H NMR (500 MHz, CDCl3): 3.21 (s, 3H), 3.20 (s, 3H), 2.80 (m, 1H), 2.10 to 1.80 (bm, 6H), 1.46 (s, 9H). 13C NMR (125 MHz, CDCl3): 174.9, 111.2, 80.3, 67.8, 49.2, 42.5, 37.4, 33.8, 28.3, 22.0.

Workup

  1. stirringthe reaction mixture was stirred overnight
  2. concentrationThe reaction mixture was concentrated at room temperature
  3. dissolutionthe resulting residue was dissolved in ether
  4. washwashed with saturated NaHCO3 solution
  5. dry with materialThe ethereal layer was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography (silica, 15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d5bde6c48314465dbadfcdabbeacc353
Source dataset
uspto-grants-2008_08
Patent number
US07410961B2

Reaction notes

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