Trifluoroacetic acid → HCID 71247172, compound

HRID 715067Notes

Reaction equation

HRID 715067 reaction equation
[F:1][C:2](=[CH2:7])[C:3]([O:5][CH3:6])=[O:4].[CH2:8]([N:15]([CH2:19][Si](C)(C)C)[CH2:16]OC)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:8]([N:15]1[CH2:16][CH2:7][C:2]([F:1])([C:3]([O:5][CH3:6])=[O:4])[CH2:19]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 2782524methyl 2-fluoroacrylate

Product 1

HCID 71247172HCID 71247172, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 0.3 M solution of methyl 2-fluoroacrylate (4.37 g, 41.99 mmol) and DCM (140 mL) was stirred under nitrogen and cooled to 0° C. The reaction mixture was then treated with N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (10.47 g, 44.09 mmol) followed by TFA (1.56 mL, 20.99 mmol). The reaction mixture was warmed to RT and stirred for 16 h. The reaction mixture was then concentrated in vacuo. The crude product was purified by SiO2 Biotage chromatography (hexanes/acetone) to afford 4.24 g (42.6%) of methyl 1-benzyl-3-fluoropyrrolidine-3-carboxylate (72a): 1H NMR (400 MHz, DMSO-d6) δ=7.35-7.23 (m, 5H), 3.72 (s, 3H), 3.63 (s, 2H), 2.97-2.80 (m, 3H), 2.54-2.48 (m, 1H), 2.43-2.30 (m, 1H), 2.18-2.04 (m, 1H).

Workup

  1. temperatureThe reaction mixture was warmed to RT
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. customThe crude product was purified by SiO2 Biotage chromatography (hexanes/acetone)

Sources & evidence

ORD record
ord-c6e53bcc83a04966a07ab239ac718eb3
Source dataset
uspto-grants-2015_11
Patent number
US09187462B2

Reaction notes

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