Tetrahydrofuran → 1-Boc-6'-bromo-1'-oxo-1',3'-dihydrospiro[azetidine-3,2'-indene]

HRID 1503455Notes

Reaction equation

HRID 1503455 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][C:7]2([C:18]#N)[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8]2)=[C:4](I)[CH:3]=1.[Li]CCCC.C1C[O:31]CC1>>[Br:1][C:2]1[CH:21]=[C:20]2[C:5]([CH2:6][C:7]3([CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8]3)[C:18]2=[O:31])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 58197573Tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 581983161-Boc-6'-bromo-1'-oxo-1',3'-dihydrospiro[azetidine-3,2'-indene]Yield 54%

Procedure

To a solution of tert-butyl 3-(4-bromo-2-iodobenzyl)-3-cyanoazetidine-1-carboxylate (4.2876 g, 8.99 mmol) in THF (120 mL) was added n-BuLi (2.5 Min hexane, 3.8 mL, 9.5 mmol) at −78° C. dropwise over 10 min under nitrogen. After 1 h, the reaction mixture was quenched with saturated NH4Cl, diluted with CH2Cl2, 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 1.7020 g (54%) of tert-butyl 6′-bromo-1′-oxo-1′,3′-dihydrospiro[azetidine-3,2′-indene]-1-carboxylate as a solid. LC-MS tR=1.90 min in 3 min chromatography, m/z 352, 354 (MH+), 337, 339 (MH+-15), 296, 298 (MH+-56); 1H NMR (400 MHz, CDCl3) δ 7.91 (m, 1H), 7.74-7.71 (m, 1H), 7.35 (d, J=7.9 Hz, 1H), 4.23 (d, J=8.2 Hz, 2H), 3.88 (d, J=8.2 Hz, 2H), 3.40 (s, 2H), 1.46 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 204.38, 156.03, 150.44, 138.17, 137.24, 127.88, 127.29, 122.19, 80.05, 57.88, 44.70, 39.67, 28.35.

Workup

  1. customthe reaction mixture was quenched with saturated NH4Cl
  2. additiondiluted with CH2Cl2
  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-c66911abc0ef41d0bc750da7db3a62d7
Source dataset
uspto-grants-2015_12
Patent number
US09212153B2

Reaction notes

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