Hydrochloric Acid → 1-Benzyl-4-(4-amino-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester

HRID 1266464Notes

Reaction equation

HRID 1266464 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=2)[CH2:9][N:8]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:7]1)=[O:5])[CH3:2].[Sn].Cl.C(=O)([O-])[O-].[Na+].[Na+]>O.C(O)C>[CH2:1]([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=2)[CH2:9][N:8]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 4151186Ethyl 1-benzyl-4-(4-nitrophenyl)pyrrolidine-3-carboxylateHCID 5352426Tin atom

Product 1

HCID 536986181-Benzyl-4-(4-amino-phenyl)-pyrrolidine-3-carboxylic acid ethyl esterYield 52.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 1-benzyl-4-(4-nitro-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (15 g, Reference Example 6), tin (25.12 g), hydrochloric acid (230 mL, 3M) and ethanol (230 mL) was heated at reflux temperature for 1 hour. After cooling to room temperature the pH of the mixture was adjusted to 9 by addition of solid sodium carbonate. The mixture was then diluted with water to give a final volume of 1000 mL and then filtered through a pad of celite. The clear filtrate was extracted twice with ethyl acetate (1000 mL). The combined extracts were dried over magnesium sulfate and then evaporated. The crude residue was subjected to chromatography using a Prochrom LC60 column, 40 cm silica bed, 20-45 μm, eluting with a mixture of cyclohexane and ethyl acetate (70:30, v/v) at 100 cm3/minute flow rate. The fractions containing the compound with RF=60/171 (thin layer chromatography plate ref. #05719, Merck KGaA, 64271 Darmstatd, Germany, cyclohexane:ethyl acetate, 70:30, v/v) were pooled and concentrated under reduced pressure (2.7 kPa) to give the title compound (7.22 g) as a yellow oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 1 hour
  3. customto give a final volume of 1000 mL
  4. filtrationfiltered through a pad of celite
  5. extractionThe clear filtrate was extracted twice with ethyl acetate (1000 mL)
  6. dry with materialThe combined extracts were dried over magnesium sulfate
  7. customevaporated
  8. washeluting with a mixture of cyclohexane and ethyl acetate (70:30, v/v) at 100 cm3/minute flow rate
  9. additionThe fractions containing the compound with RF=60/171 (thin layer chromatography plate ref. #05719, Merck KGaA, 64271 Darmstatd, Germany, cyclohexane:ethyl acetate, 70:30, v/v)
  10. concentrationconcentrated under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-b0cf331c5a944c518d18ab530e41578a
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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