Triphenylphosphine → N-tert-Butoxycarbonyl-cis-4-Hydroxy-L-Proline 3-Quinolylamide

HRID 2185399Notes

Reaction equation

HRID 2185399 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[C:34]([NH:42][C:43](=[O:57])[C@@H:44]2[CH2:48][C@@H:47]([OH:49])[CH2:46][N:45]2[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH:33]=1.[OH-].[Na+]>O1CCCC1.O.C(O)=O>[N:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[C:34]([NH:42][C:43](=[O:57])[C@@H:44]2[CH2:48][C@H:47]([OH:49])[CH2:46][N:45]2[C:50]([O:52][C:53]([CH3:55])([CH3:54])[CH3:56])=[O:51])[CH:33]=1

Participants

8

Reactant 4

HCID 11776Triphenylphosphine2×HCID 14798Sodium HydroxideHCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 70176198trans-4-Hydroxy-N-tert-Butoxycarbonyl-L-Proline 3-Quinolylamide

Product 1

HCID 53656843N-tert-Butoxycarbonyl-cis-4-Hydroxy-L-Proline 3-Quinolylamide

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (40% solution in toluene, 1.4 mL) was added to a solution of triphenylphosphine (808 mg) in tetrahydrofuran (5 mL) at ñ15° C. After stirring at −15° C. to 0° C. for 30 min, trans-4-hydroxy-N-tert-butoxycarbonyl-L-proline 3-quinolylamide (A, 729 mg), and formic acid (100 mL) were added. After stirring at room temperature for 3.5 hr, formic acid (100 mL) was added, and stirring was continued for 2 hr. Then additional Mitsunobu reagent which was prepared from triphenylphosphine (803 mg) and diethyl azodicarboxylate (40% solution in toluene, 1.4 mL) was added. After the resulting solution was stirred for 3 hr, 1 N sodium hydroxide (20 mL) was added at 0° C. and stirred at room temperature for 1.5 hr. Then water (100 mL) was added to the reaction mixture and the solvents were evaporated in vacuo. The residue was extracted with ethyl acetate and the extract was washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform then chloroform:methanol=30:1, v/v) to afford the title compound (576 mg) as a pale yellow sticky oil: 1H NMR (400 MHz, CD3OD) δ 1.3-1.6 (m, 9H), 1.9-2.2 (m, 1H), 2.3-2.6 (m, 1H), 3.4-3.7 (m, 3H), 4.24.5 (m, 1H), 7.60 (m, 1H), 7.70 (m, 1H), 7.90 (m, 1H), 7.98 (m, 1H), 8.72 (m, 1H), and 8.92 (m, 1H).

Workup

  1. stirringAfter stirring at room temperature for 3.5 hr
  2. stirringstirring
  3. waitwas continued for 2 hr
  4. additionwas added
  5. stirringAfter the resulting solution was stirred for 3 hr
  6. stirringstirred at room temperature for 1.5 hr
  7. customthe solvents were evaporated in vacuo
  8. extractionThe residue was extracted with ethyl acetate
  9. washthe extract was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customevaporated in vacuo
  12. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-1766c9ed741146e097a6ee0491034fc2
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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