Iodine → HCID 178490703, compound

HRID 76257Notes

Reaction equation

HRID 76257 reaction equation
Br[CH2:2][CH:3]1[CH2:6][CH2:5][CH2:4]1.[Mg].II.[C:10]([N:14]1[CH:18]=[C:17]([CH:19]=[O:20])/[C:16](=[N:21]/[C:22](=[O:32])[C:23]2[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])/[S:15]1)([CH3:13])([CH3:12])[CH3:11]>C1COCC1>[C:10]([N:14]1[CH:18]=[C:17]([CH:19]([OH:20])[CH2:2][CH:3]2[CH2:6][CH2:5][CH2:4]2)/[C:16](=[N:21]/[C:22](=[O:32])[C:23]2[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])/[S:15]1)([CH3:13])([CH3:12])[CH3:11]

Participants

6

Reactant 4

HCID 807IodineHCID 2734658(Bromomethyl)cyclobutaneHCID 5462224MagnesiumHCID 178490700HCID 178490700, compound

Product 1

HCID 178490703HCID 178490703, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To (bromomethyl)cyclobutane (211 mg, 1.42 mmol) in THF (20 mL) was added magnesium (41.3 mg, 1.7 mmol), and initiator iodine (10 mg). The mixture was stirred at rt for 2 hrs, then cooled to −40° C. and added to a solution of Example 21A (100 mg, 0.28 mmol) in THF (20 mL). The mixture was allowed to warm to room temperature, quenched with saturated aqueous NH4Cl, and extracted with EtOAc (2×). The organics were combined, dried (MgSO4), filtered and solvent evaporated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% Hexane in ethyl acetate) to afford 63 mg (53%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.62-1.78 (m, 2 H) 1.65 (s, 9 H) 1.76-1.94 (m, 2 H) 1.97-2.18 (m, 4 H) 2.47-2.59 (m, 1 H) 3.92 (s, 3 H) 4.88 (dd, J=8.29, 6.14 Hz, 1 H) 6.93 (d, J=8.90 Hz, 1 H) 7.37 (dd, J=8.90, 3.07 Hz, 1 H) 7.95 (s, 1 H) 8.05 (d, J=2.76 Hz, 1 H); MS (DCI/NH4+) m/z 423 (M+H)+.

Workup

  1. temperaturecooled to −40° C.
  2. temperatureto warm to room temperature
  3. customquenched with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc (2×)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customsolvent evaporated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-dcb3816657c6423bb7d60e30145bf6c9
Source dataset
uspto-grants-2014_09
Patent number
US08835475B2

Reaction notes

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