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

HRID 2223759Notes

Reaction equation

HRID 2223759 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].C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27].Cl>C1(C)C=CC=CC=1.COCCOC>[CH3:25][S:26]([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:28])=[O:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 23093714HCID 23093714, compound

Product 1

HCID 230937152-Cyano-4,5-diethoxy-3-fluorobenzyl methanesulfonate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
20 °C

Procedure

3,4-Diethoxy-2-fluoro-6-(hydroxymethyl)benzonitrile (4.50 kg, 18.81 mol) and 1,2-dimethoxyethane (45 L) were loaded into a reaction vessel, followed by stirring. The reaction solution was cooled, and the system was placed under nitrogen atmosphere. At an internal temperature of 8.4° C., triethylamine (2.47 kg, 24.45 mol) was added. Furthermore, methanesulfonyl chloride (2.59 kg, 22.61 mol) was added dropwise without warming the internal temperature over 20° C. After stirring for 34 minutes, the system was placed under a stream of nitrogen gas, and the cooling was stopped. Toluene (45 L) and 0.5 N hydrochloric acid (9 L) were added, and the solution was separated. The obtained organic layer was washed with water (18 L), 10% aqueous sodium hydrogen carbonate solution (18 L), 10% brine (18 L), and water (18 L), and the organic layer was concentrated under reduced pressure. After adding toluene (45 L) to the concentrated solution, this was concentrated again under reduced pressure. The concentrated solution was cooled and diluted with toluene (40 L), and the diluted solution from the reaction vessel was equally divided into two containers. The walls of the reaction vessel were rinsed with toluene (5 L). This rinsing solution was divided in half and mixed with the aforementioned diluted solutions to give toluene solutions of 2-cyano-4,5-diethoxy-3-fluorobenzyl methanesulfonate. They were named solution A and solution B, and after measuring the weight of the solutions (solution A; 32.16 kg, solution B: 32.24 kg), the solutions were sampled and quantified by HPLC.

Workup

  1. temperatureThe reaction solution was cooled
  2. stirringAfter stirring for 34 minutes
  3. customthe solution was separated
  4. washThe obtained organic layer was washed with water (18 L), 10% aqueous sodium hydrogen carbonate solution (18 L), 10% brine (18 L), and water (18 L)
  5. concentrationthe organic layer was concentrated under reduced pressure
  6. additionAfter adding toluene (45 L) to the concentrated solution
  7. concentrationthis was concentrated again under reduced pressure
  8. temperatureThe concentrated solution was cooled
  9. additiondiluted with toluene (40 L)
  10. washThe walls of the reaction vessel were rinsed with toluene (5 L)
  11. additionmixed with the aforementioned diluted solutions

Sources & evidence

ORD record
ord-e24455d904694e7f80163f25f1dd3b21
Source dataset
uspto-grants-2008_05
Patent number
US07375236B2

Reaction notes

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