Benzyl Bromide → HCID 86723603, compound

HRID 590667Notes

Reaction equation

HRID 590667 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([CH2:13][CH3:14])[CH2:10][C@H:9]1[C:15]([OH:17])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:18]1[CH:23]=[CH:22][C:21]([CH2:24]Br)=[CH:20][CH:19]=1>C1COCC1>[CH2:13]([CH:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([C:15]([O:17][CH2:24][C:21]2[CH:22]=[CH:23][CH:18]=[CH:19][CH:20]=2)=[O:16])[CH2:10]1)[CH3:14]

Participants

4

Reactant 2

HCID 7498Benzyl BromideHCID 86723602HCID 86723602, compound

Product 1

HCID 86723603HCID 86723603, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2S)-1-(tert-butoxycarbonyl)-4-ethylpyrrolidine-2-carboxylic acid (45.5 g, 187 mmol), TEA (37.8 g, 374 mmol) in THF (1 L) was added dropwise BnBr (38.5 g, 225 mmol) at 0° C. The mixture was stirred at room temperature overnight. TLC showed the reaction was completed. The mixture was concentrated to remove solvent. The residue was partitioned between EtOAc and water. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography to give (2S)-2-benzyl 1-tert-butyl 4-ethylpyrrolidine-1,2-dicarboxylate (46 g, 74%) as colorless oil. (2S)-2-benzyl 1-tert-butyl 4-ethylpyrrolidine-1,2-dicarboxylate was separated by preparative SFC via a Chiralcel OD 250*50 mm i.d. 10 μm column (Mobile phase: A for n-hexane and B for ethanol (0.05% IPAm), Gradient: A: B=97:3, Flow rate: 100 ml/min, Wavelength: 210 and 220 nm, Injection amount: 0.4 g per injection) to provide (2S,4S)-2-benzyl 1-tert-butyl 4-ethylpyrrolidine-1,2-dicarboxylate.

Workup

  1. concentrationThe mixture was concentrated
  2. customto remove solvent
  3. customThe residue was partitioned between EtOAc and water
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-e503c40fcc004bda814469b5a8629b70
Source dataset
uspto-grants-2016_01
Patent number
US09233974B2

Reaction notes

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