Allyl bromide → (2S,3R)-3-But-3-enyl-1-((S)-1-phenyl-ethyl)-pyrrolidine-2-carboxylic acid ethyl ester

HRID 29062Notes

Reaction equation

HRID 29062 reaction equation
[Li+].[CH3:2][CH:3]([N-]C(C)C)[CH3:4].[CH2:9]([O:11][C:12](=[O:27])[CH2:13][N:14]([CH2:23][CH2:24][CH:25]=[CH2:26])[C@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])[CH3:10].C([Cu])#N.[Li+].[Cl-].C(Br)C=C>C1COCC1.CCOCC.[Zn+2].[Br-].[Br-]>[CH2:9]([O:11][C:12]([C@@H:13]1[C@H:25]([CH2:26][CH2:4][CH:3]=[CH2:2])[CH2:24][CH2:23][N:14]1[C@H:15]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:16])=[O:27])[CH3:10]

Participants

9

Reactant 5

HCID 7841Allyl bromideHCID 433294Lithium ChlorideHCID 2724682Lithium diisopropylamideHCID 10956339(s)-[But-3-enyl-(1-phenyl-ethyl)-amino]-acetic acid ethyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 67003902(2S,3R)-3-But-3-enyl-1-((S)-1-phenyl-ethyl)-pyrrolidine-2-carboxylic acid ethyl esterYield 82.6%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of diisopropylamine(3.6 g, 35.7 mmol) in THF(80 mL) at −40° C. is added BuLi(14.28 mL, 35.7 mmol, 2.5 M in hexane) slowly. The solution is warmed to 0° C. and stirred for 30 min to form an LDA solution. The LDA solution is cooled to −70° C. and added to a solution of [But-3-enyl-((S)-1-phenyl-ethyl)-amino]-acetic acid ethyl ester(7.8 g, 29.8 mmol) in THF (80 mL) slowly at −70° C. The light yellowish reaction solution is stirred at −20° C. for 30 min to become a deep yellow solution, and then cooled to −70° C. To the solution is added **ZnBr2**(16.76 g, 74.5 mmol) in ether (50 mL) dropwise at −70° C. After stirring at RT for 1.5 hrs, the reaction solution is cooled to 0° C. and added a solution of CuCN(3.47 g, 38.74 mmol) and LiCl(3.29 g, 77.48 mmol) in THF(80 mL) slowly. After stirring at 0° C. for 10 min, allyl bromide(7.26 g, 60 mmol) is added dropwise to the reaction solution, and warmed very slowly to r.t. After stirring overnight at r.t., the reaction is quenched by addition of 60 mL of saturated NH4Cl and extracted with 3×150 mL of ether. The combined organic layers is concentrated. The crude product is purified by chromatography (hexane/EtOAc: 85/15) to give a colorless liquid(7.4 g, 82.6%). (NMR and MS data confirmed, U-4117-40-19, U-4117-34-35). ** ZnBr2** is dried at 150° C. under high vacuum for 1 hour before used**

Workup

  1. temperaturecooled to −70° C
  2. stirringAfter stirring at RT for 1.5 hrs
  3. temperaturethe reaction solution is cooled to 0° C.
  4. stirringAfter stirring at 0° C. for 10 min
  5. temperaturewarmed very slowly to r.t
  6. stirringAfter stirring overnight at r.t.
  7. customthe reaction is quenched by addition of 60 mL of saturated NH4Cl
  8. extractionextracted with 3×150 mL of ether
  9. concentrationThe combined organic layers is concentrated
  10. customThe crude product is purified by chromatography (hexane/EtOAc: 85/15)

Sources & evidence

ORD record
ord-9b0eff8b36f844b5ae9b2216ffd46532
Source dataset
uspto-grants-2008_09
Patent number
US07419975B2

Reaction notes

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