Triphenylsilane → (2S,5S)-2-But-3-enyl-5-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1261855Notes

Reaction equation

HRID 1261855 reaction equation
C([O:8][C:9](=O)[C@@H:10]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:11][CH2:12][C:13](=O)[CH2:14][CH2:15][CH:16]=[CH2:17])C1C=CC=CC=1.C1([SiH](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC1C(B(C2C(F)=C(F)C(F)=C(F)C=2F)C2C(F)=C(F)C(F)=C(F)C=2F)=C(F)C(F)=C(F)C=1F.C(OC(N1[C@@H](CCC=C)CC[C@H]1C(OCC1C=CC=CC=1)=O)=O)(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(Cl)Cl.C1COCC1>[C:23]([O:22][C:20]([N:19]1[C@H:10]([CH2:9][OH:8])[CH2:11][CH2:12][C@@H:13]1[CH2:14][CH2:15][CH:16]=[CH2:17])=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 5

HCID 69922Triphenylsilane2×HCID 582056Tris(pentafluorophenyl)borane2×HCID 21226445Aluminium lithium hydrideHCID 67092604(S)-2-tert-Butoxycarbonylamino-5-oxo-non-8-enoic acid benzyl esterHCID 67093063(2S,5S)-5-but-3-enyl-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

Product 1

HCID 67092700(2S,5S)-2-But-3-enyl-5-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (S)-2-tert-butoxycarbonylamino-5-oxo-non-8-enoic acid benzyl ester in DCM (5 mL) was added at −78° C. to a solution of triphenylsilane (496 mg, 1.90 mmol) and tris(pentafluorophenyl)borane (55 mg, 0.11 mmol) in DCM (5 mL), then after 30 min the cooling bath was removed and the reaction mixture was allowed to reach room temperature over 2 h. After cooling to −78° C. a solution of triphenylsilane (496 mg, 1.90 mmol) and tris(pentafluorophenyl)borane (55 mg, 0.11 mmol) in DCM (5 mL) was added to the reaction mixture, then after 30 min the cooling bath was removed. The reaction mixture was stirred at room temperature for 72 h, then treated with Et3N (1 mL), then after 20 min partitioned between sat. aq. ammonium chloride solution and EtOAc. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane/EtOAc3:1) afforded an inseparable mixture of (2S,5S)-5-but-3-enyl-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester and unspecified reagents. This mixture was dissolved in THF (2.5 mL) and added dropwise at 0° C. to a suspension of lithium aluminum hydride (65 mg, 1.71 mmol) in THF (2.5 mL), then after 20 min excess reagent was destroyed by addition of water (2 mL), EtOAc and 2 M aq. sodium hydroxide solution (1 mL). The reaction mixture was filtered through diatomaceous earth, the filtrate was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane/EtOAc 3:1) afforded the title compound (179 mg, 82%). Colourless oil, MS: 256.3 (M+H)+.

Workup

  1. customafter 30 min the cooling bath was removed
  2. additionwas added to the reaction mixture
  3. customafter 30 min the cooling bath was removed
  4. additiontreated with Et3N (1 mL)
  5. customafter 20 min partitioned between sat. aq. ammonium chloride solution and EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customChromatography (SiO2; heptane/EtOAc3:1) afforded
  11. customafter 20 min excess reagent was destroyed by addition of water (2 mL), EtOAc and 2 M aq. sodium hydroxide solution (1 mL)
  12. filtrationThe reaction mixture was filtered through diatomaceous earth
  13. washthe filtrate was washed with brine
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-10404a704e3e4894bc2bd540ba6eefb1
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

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