Iodine → HCID 67504868, compound

HRID 2408490Notes

Reaction equation

HRID 2408490 reaction equation
II.BrCCBr.Cl[CH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH3:14][O:15][C:16]1[N:21]=[CH:20][C:19](/[CH:22]=[N:23]/[S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])=[CH:18][CH:17]=1>C1COCC1.C1(C)C=CC=CC=1>[CH3:14][O:15][C:16]1[N:21]=[CH:20][C:19]([CH:22]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[NH:23][S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 807IodineHCID 78391,2-DibromoethaneHCID 1372022H-Pyran, 4-chlorotetrahydro-HCID 87424661HCID 87424661, compound

Product 1

HCID 67504868HCID 67504868, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

Mg (10.6 g, 438 mmol) was dispersed in THF (160 mL) and 1 crystal of I2 and 1,2-dibromoethane (0.25 mL) were added. 4-Chlorotetrahydro-2H-pyran, dissolved in THF (50 mL), was added dropwise and the mixture was heated at 70° C. for 1.5 h. The solution was cooled to 0° C. and the product from step A was added dropwise as a solution in toluene (100 mL). The reaction was aged at rt for 2 h and the mixture was filtered eluting with MTBE. The reaction was quenched with sat. NH4Cl (aq) and extracted twice with EtOAc. The organic layers were combined and washed with brine, dried with Na2SO4, filtered and concentrated. The resulting oil was purified by flash chromatography on silica gel gradient eluted with 100% EtOAc to 8% MeOH in EtOAc affording the desired slow eluting diastereomer, (B-1). HPLC/MS: 327.1 (M+1); Rt=231 min. The fast eluting isomer on silica gel (B-2) was also isolated. HPLC/MS: 327.1 (M+1); Rt=2.15 min

Workup

  1. additionwas added dropwise
  2. temperatureThe solution was cooled to 0° C.
  3. filtrationthe mixture was filtered
  4. washeluting with MTBE
  5. customThe reaction was quenched with sat. NH4Cl (aq)
  6. extractionextracted twice with EtOAc
  7. washwashed with brine
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting oil was purified by flash chromatography on silica gel gradient
  12. washeluted with 100% EtOAc to 8% MeOH in EtOAc affording the desired slow eluting diastereomer, (B-1)
  13. customThe fast eluting isomer on silica gel (B-2) was also isolated

Sources & evidence

ORD record
ord-43ba0d628f2441118a5f86c2e6fca8c0
Source dataset
uspto-grants-2014_08
Patent number
US08815865B2

Reaction notes

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