Bromocyclobutane → HCID 59536623, compound

HRID 1922164Notes

Reaction equation

HRID 1922164 reaction equation
[Mg].[CH:2]1(Br)[CH2:5][CH2:4][CH2:3]1.[C:7]([O:11][C:12]([N:14]1[CH2:18][CH2:17][C@H:16]([C:19](=[O:24])N(OC)C)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>C1COCC1.[H-].C([Al+]CC(C)C)C(C)C.II>[C:7]([O:11][C:12]([N:14]1[CH2:18][CH2:17][C@H:16]([C:19]([CH:2]2[CH2:5][CH2:4][CH2:3]2)=[O:24])[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 3

HCID 78110BromocyclobutaneHCID 5462224Magnesium2×HCID 59163141HCID 59163141, compound

Product 1

HCID 59536623HCID 59536623, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 21225700DiisobutylaluminumhydrideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

Add diisobutylaluminium hydride (1M in toluene, 0.790 mL, 0.790 mmol) to a stirred mixture of magnesium (0.960 g, 39.5 mmol) and iodine (0.100 g, 0.395 mmol) in THF (1 mL) under nitrogen. Add drop wise a solution of cyclobutyl bromide (8.00 g, 59.2 mmol) in THF (10 mL) and stir the reaction at 60° C. for 2 h whereby all the magnesium is consumed. Cool the mixture to room temperature and add drop wise a solution of (S)-3-(methoxy(methyl)carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (10.2 g, 39.5 mmol) in THF (50 mL). Stir the reaction mixture at room temperature for 2.5 h. Quench with 1 M aqueous citric acid, extract with EtOAc. Wash the organic layer with water and saturated aqueous NaCl, dry (Na2SO4), filter and concentrate under reduced pressure. Purify the residue by silica gel chromatography, eluting with EtOAc in hexanes (0-50% gradient) to obtain the title compound (5.30 g, 53%).

Workup

  1. customis consumed
  2. stirringStir the reaction mixture at room temperature for 2.5 h
  3. customQuench with 1 M aqueous citric acid
  4. extractionextract with EtOAc
  5. washWash the organic layer with water and saturated aqueous NaCl
  6. dry with materialdry (Na2SO4)
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue by silica gel chromatography
  10. washeluting with EtOAc in hexanes (0-50% gradient)

Sources & evidence

ORD record
ord-c9843b4b3158451587ffc0dd17f5e264
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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