Tetrahydrofuran → tert-butyl N-Boc-4-methylene-L-prolinate

HRID 399530Notes

Reaction equation

HRID 399530 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:22])[C@@H:9]1[CH2:13][C:12](=O)[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:6])([CH3:5])[CH3:4].[CH2:23]1COCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:3]([O:7][C:8](=[O:22])[C@@H:9]1[CH2:13][C:12](=[CH2:23])[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 11346670(S)-di-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 18665883tert-butyl N-Boc-4-methylene-L-prolinate

Reagents, catalysts & solvents 1

HCID 74505Methyltriphenyliphosphonium bromideCatalyst

Procedure

To an oven-dried 2-necked round-bottomed flask was added sodium hydride (80% oil dispersion) (497 mg, 16.56 mmol) followed by dry tetrahydrofuran (42 mL) and methyltriphenyl-phosphonium bromide (5.92 g, 16.56 mmol). The suspension was stirred for 4 hours at 50° C., at which time a solution of 1-(tert-butyloxycarbonyl)-4-oxo-L-proline tert-butyl ester (1.18 g, 4.14 mmol) in THF (10 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was stirred for 2 hours at 50° C., cooled, filtered, and evaporated. The residue was taken up in ethyl acetate (100 mL), washed with N hydrochloric acid (2×), water (2×), saturated brine solution, dried (Na2SO4), and evaporated. The crude product was subjected to flash silica gel chromatography eluting with 15% diethyl ether/hexane. The title compound was obtained as a colorless oil; yield 519 mg (43%). 400 MHz 1HNMR (CDCl3): δ1.42-1.47 (3s, 18H); 2.54 (m, 1H); 2.92 (m, 1H); 4.03 (m, 2H); 4.23-4.38 (m, 1H); 4.98 (m, 2H).

Workup

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred for 2 hours at 50° C.
  3. temperaturecooled
  4. filtrationfiltered
  5. customevaporated
  6. washwashed with N hydrochloric acid (2×), water (2×), saturated brine solution
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. washeluting with 15% diethyl ether/hexane

Sources & evidence

ORD record
ord-e61b550a564045f2b735f3c5240b813c
Source dataset
uspto-grants-1998_10
Patent number
US05821261

Reaction notes

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