Hydrochloric Acid → 2-Cyano-4,5-diethoxy-3-fluorobenzyl methanesulfonate

HRID 2223760Notes

Reaction equation

[CH2:1]([O:3][C:4]1[C:5]([F:17])=[C:6]([C:9]([CH2:15][OH:16])=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:7]#[N:8])[CH3:2].[CH3:18][S:19](Cl)(=[O:21])=[O:20].C(N(CC)CC)C.Cl>COCCOC.C1(C)C=CC=CC=1>[CH3:18][S:19]([O:16][CH2:15][C:9]1[CH:10]=[C:11]([O:12][CH2:13][CH3:14])[C:4]([O:3][CH2:1][CH3:2])=[C:5]([F:17])[C:6]=1[C:7]#[N:8])(=[O:21])=[O:20]

Participants

Conditions

Temperature: 8 °C

Procedure

3,4-Diethoxy-2-fluoro-6-(hydroxymethyl)benzonitrile (1 g, 4.18 mmol) was dissolved in 1,2-dimethoxyethane (10 mL), and cooled in a constant temperature bath at 8° C. after addition of methanesulfonyl chloride (0.39 mL, 5.02 mmol). Triethylamine (0.76 mL, 5.43 mmol) was added dropwise to this solution at approximately 20° C. or less. After stirring at the same temperature for 1 hour, toluene (5 mL) and 0.5 N hydrochloric acid (2 mL) were added, and this was transferred to a separatory funnel and toluene (5 mL) was used for rinsing. After separation of the solution, sequential washing was carried out with water (4 mL), 10% aqueous sodium hydrogen carbonate solution (4 mL), 10% brine (4 mL), and water (4mL). After the organic layer was evaporated, toluene (4 mL) was added, and water was removed by azeotropic distillation. Toluene (4 mL) was added to the residue and this was used in the next step. HPLC analytical values for the toluene solution: 99.10% (toluene peak is disregarded).

Workup

customthis was transferred to a separatory funnel
washfor rinsing
customAfter separation of the solution, sequential
washwashing
customAfter the organic layer was evaporated
additiontoluene (4 mL) was added
customwater was removed by azeotropic distillation
additionToluene (4 mL) was added to the residue

Sources & evidence

ORD record: ord-5c4e3441c1954cb5a0f09ab5a1d245bb
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07375236B2

Reaction notes

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