Trifluoroacetic acid → 5-(3-methoxyphenyl)-3,4-dihydro-2H-pyrrole

HRID 1157656Notes

Reaction equation

HRID 1157656 reaction equation
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][CH2:15][CH2:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=1)=O)(C)(C)C.[OH-].[Na+]>>[CH3:27][O:26][C:22]1[CH:21]=[C:20]([C:18]2[CH2:17][CH2:16][CH2:15][N:14]=2)[CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 59511949tert-butyl N-[4-(3-methoxyphenyl)-4-oxobutyl]carbamate

Product 1

HCID 120090515-(3-methoxyphenyl)-3,4-dihydro-2H-pyrroleYield 91.7%

Conditions

Temperature
0 °C

Procedure

Add trifluoroacetic acid (49.8 mL, 670 mmol) to [4-(3-methoxy-phenyl)-4-oxo-butyl]-carbamic acid tert-butyl ester (22.21 g, 67 mmol) with ice/water cooling. After stirring at 0° C. for 3.5 h, adjust the reaction to pH 10 with 50% sodium hydroxide. Extract the reaction mixture with ether (5×100 mL), dry the combined organic layers over magnesium sulfate, filter, and concentrate under reduced pressure to obtain the crude product (15.43 g). Purify by flash chromatography [silica gel, 330 g, 0 to 30% gradient of (90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) in methylene chloride] to obtain the title compound (10.76 g, 88% for two steps). MS (APCI+): 176 [C11H13NO+H]+; 1H NMR (300 MHz, CDCl3): δ 7.46-7.45 (m, 1H), 7.37-7.27 (m, 2H), 6.99-6.95 (m, 1H), 4.09-4.03 (m, 2H), 3.84 (s, 3H), 2.96-2.89 (m, 2H), 2.08-1.97 (m, 2H).

Workup

  1. extractionExtract the reaction mixture with ether (5×100 mL)
  2. dry with materialdry the combined organic layers over magnesium sulfate
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customto obtain the crude product (15.43 g)
  6. customPurify by flash chromatography [silica gel, 330 g, 0 to 30% gradient of (90:10:1 methylene chloride/methanol/concentrated ammonium hydroxide) in methylene chloride]

Sources & evidence

ORD record
ord-a2ed30eb748341b29a7d93c65a308355
Source dataset
uspto-grants-2010_10
Patent number
US07807691B2

Reaction notes

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