Triethylamine → 4-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2,5-difluoro-3-methoxybenzoic acid ethyl ester

HRID 10284

Reaction equation

HRID 10284 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[C:9]([F:11])[C:8](F)=[C:7]([O:13][CH3:14])[C:6]=1[F:15])[CH3:2].[C:17]([O:21][C:22](=[O:29])[NH:23][CH:24]1[CH2:28][CH2:27][NH:26][CH2:25]1)([CH3:20])([CH3:19])[CH3:18].C(N(CC)CC)C>C(#N)C>[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([N:26]2[CH2:27][CH2:28][CH:24]([NH:23][C:22]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:29])[CH2:25]2)=[C:7]([O:13][CH3:14])[C:6]=1[F:15])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 2774387Benzoic acid, 2,4,5-trifluoro-3-methoxy-, ethyl ester

Product 1

HCID 210411814-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-2,5-difluoro-3-methoxybenzoic acid ethyl esterYield 77.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,4,5-trifluoro-3-methoxybenzoic acid ethyl ester (Example 1f, 2.821 g, 12.05 mmol), pyrrolidin-3-ylcarbamic acid tert-butyl ester (3.310 g, 17.77 mmol), and triethylamine (9.13 g, 12.6 mL, 90.23 mmol) in acetonitrile (50 mL) is heated at 40° C. under nitrogen for 2 days. The yellow solution is concentrated to near dryness and poured into saturated NaHCO3 solution and extracted with dichloromethane. The combined organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The resulting residue is purified by flash column chromatography (1:7 ethyl acetate/hexanes) to afford the title compound as a yellow solid (3.743 g). MS EI: m/z 401 (MH+).

Workup

  1. concentrationThe yellow solution is concentrated
  2. additionpoured into saturated NaHCO3 solution
  3. extractionextracted with dichloromethane
  4. washThe combined organic extracts are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe resulting residue is purified by flash column chromatography (1:7 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f2ce1d24c4af410d90ca4f96147cdb48
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Linked notes

Loading…