Trimethyl orthoformate → Tert-butyl 3,3-dimethoxycyclopentanecarboxylate

HRID 643522Notes

Reaction equation

HRID 643522 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 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrate2×HCID 14009986tert-Butyl 3-oxocyclopentane-1-carboxylate

Product 1

HCID 58784445Tert-butyl 3,3-dimethoxycyclopentanecarboxylate

Reagents, catalysts & solvents 1

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 rt 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 rt 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 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 rt
  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-3770f833ad154dd092274b232c7d66f5
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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