Triethylamine → (S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl-2,3,5,6-tetrafluorobenzoic acid benzyl ester

HRID 10282

Reaction equation

HRID 10282 reaction equation
[CH2:1]([O:8][C:9](=[O:21])[C:10]1[C:15]([F:16])=[C:14]([F:17])[C:13](F)=[C:12]([F:19])[C:11]=1[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:29]([O:33][C:34](=[O:41])[NH:35][C@H:36]1[CH2:40][CH2:39][NH:38][CH2:37]1)([CH3:32])([CH3:31])[CH3:30]>C(#N)C>[CH2:1]([O:8][C:9](=[O:21])[C:10]1[C:11]([F:20])=[C:12]([F:19])[C:13]([N:38]2[CH2:39][CH2:40][C@H:36]([NH:35][C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:41])[CH2:37]2)=[C:14]([F:17])[C:15]=1[F:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 517856Pentafluorobenzoic acid, benzyl esterHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine

Product 1

HCID 86607128(S)-3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl-2,3,5,6-tetrafluorobenzoic acid benzyl esterYield 63.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2,3,4,5,6-pentafluorobenzoic acid benzyl ester (Example 1d, 8.05 g, 26.6 mmol), triethylamine (26 mL, 186 mmol), and (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (5.6 g, 30 mmol) in acetonitrile (150 mL) is stirred at room temperature for 24 hours. The solvent is removed under vacuum and the residue dissolved in chloroform, washed with NaHCO3 and then brine, dried over Na2SO4, filtered, and concentrated in vacuo to afford a solid. The solid is then purified by column chromatography (1:1:6 ethyl acetate/chloroform/hexanes) to yield the title compound as a solid (7.92 g). 1H NMR (CDCl3): δ 7.48–7.30 (m, 5H), 5.35 (s, 2H), 4.77–4.50 (m, 1H), 4.37–4.19 (m, 1H), 4.01–3.63 (m, 3H), 3.59–3.46 (m, 1H), 2.29–2.09 (m, 1H), 2.01–1.82 (m, 1H), 1.45 (s, 9H).

Workup

  1. customThe solvent is removed under vacuum
  2. dissolutionthe residue dissolved in chloroform
  3. washwashed with NaHCO3
  4. dry with materialbrine, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a solid
  8. customThe solid is then purified by column chromatography (1:1:6 ethyl acetate/chloroform/hexanes)

Sources & evidence

ORD record
ord-0359e6b7f9d248c590d7dedd48f39951
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Linked notes

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