Hydrochloric Acid → HCID 24851280, compound

HRID 2272809Notes

Reaction equation

HRID 2272809 reaction equation
Cl.[OH:2][C@@H:3]1[C@H:8]([OH:9])[C@@H:7]([O:10][CH3:11])[C:6]([CH3:13])([CH3:12])[O:5][C@H:4]1[O:14][C:15]1[C:24]([CH3:25])=[C:23]2[C:18]([CH:19]=[C:20]([NH:27][C:28]([C:30]3[CH:31]=[C:32]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4C)[C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)=[O:29])[C:21](=[O:26])[O:22]2)=[CH:17][CH:16]=1.[H-].[Na+].[CH:47]1C=CC(CBr)=CC=1>CO>[OH:2][C@@H:3]1[C@H:8]([OH:9])[C@@H:7]([O:10][CH3:11])[C:6]([CH3:13])([CH3:12])[O:5][C@H:4]1[O:14][C:15]1[C:24]([CH3:25])=[C:23]2[C:18]([CH:19]=[C:20]([NH:27][C:28]([C:30]3[CH:31]=[C:32]([C:38]4[CH:39]=[CH:40][CH:41]=[C:42]([CH3:47])[CH:43]=4)[C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)=[O:29])[C:21](=[O:26])[O:22]2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 24850967HCID 24850967, compound

Product 1

HCID 24851280HCID 24851280, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Hydrogen chloride was bubbled through 29 (2.00 g, 6.16 mmol) in anhydrous MeOH (44.0 mL) for three minutes at room temperature, then the solution was stirred at 50° C. for 5 minutes. The solvent was concentrated and the residue placed under high vacuum for six hours to ensure complete removal of MeOH. The yellow residue was dissolved in anhydrous dimethylformamide (44.0 mL) and cooled to 0° C., then NaH (997 mg, 24.93 mmol) was added. After 15 minutes, BnBr (1.20 mL, 1.73 g, 10.09 mmol) was added and the reaction was warmed to room temperature over 18 hours. Reaction contents were partitioned between saturated aqueous NaHCO3 (500 mL) and EtOAc (500 mL), then extracted with EtOAc (3×500 mL). The combined organic layers were washed with water (3×1 L), saturated aqueous NaCl solution (1 L), dried (Na2SO4), filtered, and concentrated. The residue was purified via column chromatography (SiO2, 9:1 Hexanes:EtOAc) to give 30 as a light orange solid containing greater than 80% 3-bromo isomer (1.70 g, 88%), which was used without further purification.

Workup

  1. concentrationThe solvent was concentrated
  2. waitthe residue placed under high vacuum for six hours
  3. customremoval of MeOH
  4. dissolutionThe yellow residue was dissolved in anhydrous dimethylformamide (44.0 mL)
  5. temperaturecooled to 0° C.
  6. waitAfter 15 minutes
  7. temperaturethe reaction was warmed to room temperature over 18 hours
  8. customReaction contents
  9. customwere partitioned between saturated aqueous NaHCO3 (500 mL) and EtOAc (500 mL)
  10. extractionextracted with EtOAc (3×500 mL)
  11. washThe combined organic layers were washed with water (3×1 L), saturated aqueous NaCl solution (1 L)
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified via column chromatography (SiO2, 9:1 Hexanes:EtOAc)

Sources & evidence

ORD record
ord-6f45fae21ef4482c93bdf519aec9cb7b
Source dataset
uspto-grants-2015_09
Patent number
US09120774B2

Reaction notes

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