Lithium Hexamethyldisilazide → Tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylate

HRID 473030Notes

Reaction equation

HRID 473030 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21]Br)=[C:17]([I:23])[CH:16]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:3]2([C:1]#[N:2])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]2)=[C:17]([I:23])[CH:16]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 106312831-Boc-3-cyanoazetidineHCID 532313074-Bromo-1-(bromomethyl)-2-iodobenzene

Product 1

HCID 58197573Tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylateYield 75.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (2.1774 g, 11.95 mmol) and 4-bromo-1-(bromomethyl)-2-iodobenzene (5.0227 g, 13.36 mmol) in THF (30 mL) was added LiHMDS (1.0 Min THF, 15 mL, 15 mmol) at −78° C. The mixture was allowed to slowly warm to room temperature over 20 h. The reaction mixture was then quenched with saturated NH4Cl, extracted with EtOAc, and dried over Na2SO4. After the solvent was evaporated under reduced pressure, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 4.2959 g (75%) of tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylate as foam. LC-MS tR=2.17 min in 3 min chromatography, m/z 477, 479 (MH+), 462, 464 (MH+-15), 421, 423 (MH+-56).

Workup

  1. customThe reaction mixture was then quenched with saturated NH4Cl
  2. extractionextracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. customAfter the solvent was evaporated under reduced pressure
  5. customthe residue was purified by chromatography on silica gel
  6. washeluted with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-1e093c0edfa24f6cb7b0ed6713f9c84f
Source dataset
uspto-grants-2014_01
Patent number
US08633212B2

Reaction notes

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