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

HRID 1172884Notes

Reaction equation

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

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 the clean product (orange oil). 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
customgave the clean product (orange oil)

Sources & evidence

ORD record: ord-78fa2697d70c41df90c7c7ee8672d93d
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834034B2

Reaction notes

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