Hydrochloric Acid → 2-(2,2-Difluoro-2-(fluorosulfonyl)acetamido)ethyl methacrylate

HRID 595780

Reaction equation

HRID 595780 reaction equation
[F:1][S:2]([C:5]([F:10])([F:9])[C:6](F)=[O:7])(=[O:4])=[O:3].Cl.[C:12]([O:17][CH2:18][CH2:19][NH2:20])(=[O:16])[C:13]([CH3:15])=[CH2:14].N1C=CC=CC=1.Cl>C(Cl)Cl>[C:12]([O:17][CH2:18][CH2:19][NH:20][C:6](=[O:7])[C:5]([F:10])([F:9])[S:2]([F:1])(=[O:4])=[O:3])(=[O:16])[C:13]([CH3:15])=[CH2:14]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 69614Difluoro(fluorosulphonyl)acetyl fluorideHCID 75495Aminoethyl methacrylate hydrochloride

Product 1

HCID 1186694122-(2,2-Difluoro-2-(fluorosulfonyl)acetamido)ethyl methacrylateYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A 500 ml flask was charged with CH2Cl2 (80 ml) under nitrogen stream and stirred for 10 min at 0° C. and then 2-(fluorosulfonyl)difluoroacetyl fluoride (29.9 g, 166.0 mmol, 1.5 equivalent (eq.)) was added. After 25 minutes, a CH2Cl2 (160 ml) solution of 2-aminoethyl methacrylate hydrochloride (18.4 g, 111.0 mmol, 1.0 eq.) and pyridine (17.5 g, 221.0 mmol, 2.0 eq.) was added drop wise to the mixture over 50 minutes. The mixture was allowed to warm to room temperature (RT) and stirred for 3 hours at RT. 1N HCl was added to the final reaction mixture and the lower layer was separated and washed with 1N HCl and Brine. The solution was dried over anhydrous MgSO4, filtrated and then CH2Cl2 was removed by an evaporator. The crude product was purified by recrystallization (hexane/CHCl3). The target compound was obtained as a white solid (20.4 g) in 64% yield. 1H-NMR (400 MHz, CDCl3); delta=1.93 (dd, J=1.1, 1.2 Hz, 3H), 3.73 (td, J=5.4, 5.2 Hz, 2H), 4.35 (dd, J=5.1, 5.0 Hz, 2H), 5.63 (dq, J=1.4, 1.5 Hz, 1H), 6.12-6.14 (m, 1H), 7.09 (brs, 1H). 19F-NMR (376 MHz, CDCl3, C6F6 as standard); delta=40.68 (t, J=5.1 Hz, 1F), −105.91 (d, J=4.8 Hz, 2F).

Workup

  1. waitAfter 25 minutes
  2. temperatureto warm to room temperature (RT)
  3. stirringstirred for 3 hours at RT
  4. customreaction mixture
  5. customthe lower layer was separated
  6. washwashed with 1N HCl and Brine
  7. dry with materialThe solution was dried over anhydrous MgSO4
  8. filtrationfiltrated
  9. customCH2Cl2 was removed by an evaporator
  10. customThe crude product was purified by recrystallization (hexane/CHCl3)

Sources & evidence

ORD record
ord-b7a2bb68f4a14d5ebf11d4cfdba6b26b
Source dataset
uspto-grants-2016_01
Patent number
US09244345B1

Linked notes

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