Water → Di-tert-butyl [4-(1,3-dioxolan-2-yl)-3-fluorophenyl](methyl)malonate

HRID 500662Notes

Reaction equation

[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:8][C:7]=1[F:27].IC.[C:30](=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:30])([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[CH:8][C:7]=1[F:27]

Participants

Conditions

Temperature: 70 °C

Procedure

Di-tert-butyl [4-(1,3-dioxolan-2-yl)-3-fluorophenyl]malonate (2.45 g, 6.41 mmol), iodomethane (0.80 mL, 12.85 mmol) and potassium carbonate (1.78 g, 12.9 mmol) were suspended in DMF (10 mL) and heated at 70° C. for 3 hours in a sealed tube. A further portion of iodomethane was added (0.60 mL, 9.64 mmol) and heating continued at 75° C. for 3 hours. Room temperature was attained, H2O (150 mL) was added and the products extracted into Et2O (2×100 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC gave 0.91 g of clean product (orange oil, 36%). 1H NMR (CDCl3) δ 7.47 (t, J=8.1 Hz, 1H), 7.19 (dd, J=8.1, 1.8 Hz, 1H), 7.17 (dd, J=12.0, 1.8 Hz, 1H), 6.07 (s, 1H), 4.13 (m, 2H), 4.03 (m, 2H), 1.74 (s, 3H), 1.45 (s, 18H).

Workup

temperatureheating
customRoom temperature
extractionthe products extracted into Et2O (2×100 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue by MPLC

Sources & evidence

ORD record: ord-8b79f52572174239852966fb1ee7946c
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772238B2

Reaction notes

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