Triethylamine → 4-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2,3-difluorobenzoic acid ethyl ester

HRID 10286Notes

Reaction equation

HRID 10286 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8](F)=[C:7]([F:12])[C:6]=1[F:13])[CH3:2].[C:15]([O:19][C:20](=[O:27])[NH:21][CH:22]1[CH2:26][CH2:25][NH:24][CH2:23]1)([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C>C(#N)C>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([N:24]2[CH2:25][CH2:26][CH:22]([NH:21][C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:27])[CH2:23]2)=[C:7]([F:12])[C:6]=1[F:13])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 594559Benzoic acid, 2,3,4-trifluoro-, ethyl esterHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamate

Product 1

HCID 210411774-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2,3-difluorobenzoic acid ethyl esterYield 70.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,3,4-trifluorobenzoic acid ethyl ester (Example 1g, 3.70 g, 18.1 mmol), pyrrolidin-3-ylcarbamic acid tert-butyl ester (4.02 g, 21.6 mmol), and triethylamine (18.0 mL, 129 mmol) in acetonitrile (50 mL) is heated at 50° C. under nitrogen atmosphere for 4.5 hours. The solution is concentrated in vacuo and poured into a saturated NaHCO3 solution. The mixture is then extracted with chloroform, and the combined organic extracts are washed with brine, dried with Na2SO4, filtered, and the mixture concentrated in vacuo. The resulting residue is then purified by column chromatography (1:7 ethyl acetate/hexanes) to afford the title compound (4.70 g). 1H NMR (CDCl3): δ 7.59–7.49 (m, 1H), 6.35–6.26 (m, 1H), 4.88–4.84 (bd, 1H), 4.39–4.28 (m, 3H), 3.81–3.50 (m, 3H), 3.48–3.34 (m, 1H), 2.32–2.15 (m, 1H), 2.02–1.76 (m, 1H), 1.45 (s, 9H), 1.40 (t, 3H).

Workup

  1. concentrationThe solution is concentrated in vacuo
  2. additionpoured into a saturated NaHCO3 solution
  3. extractionThe mixture is then extracted with chloroform
  4. washthe combined organic extracts are washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationthe mixture concentrated in vacuo
  8. customThe resulting residue is then purified by column chromatography (1:7 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4cd038f4ec2c4063a2e06a388d2c39ee
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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