Iodoethane → Ethyl 7-benzyloxy-2-ethylchromane-2-carboxylate

HRID 479648Notes

Reaction equation

HRID 479648 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][CH:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)P(N(C)C)(N(C)C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].I[CH2:46][CH3:47]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH2:13][CH2:14][C:15]([CH2:46][CH3:47])([C:19]([O:21][CH2:22][CH3:23])=[O:20])[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 12679HexamethylphosphoramideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11162736Ethyl 7-(Benzyloxy)chroman-2-carboxylate

Product 1

HCID 11175194Ethyl 7-benzyloxy-2-ethylchromane-2-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 320 ml anhydrous THF solution of ethyl 7-benzyloxychromane-2-carboxyate 14.6 g (46.6 mmol) were added hexamethylphosphoramide (10.5 ml, 60.4 mmol). Upon cooling in a dry ice-acetone bath, sodium bis(trimethylsilyl)amide (1.0M/THF) (60.5 ml, 60.5 mmol) was added via syringe over 15 min period. The resulting orange solution was stirred at that temperature for 30 min before iodoethane (18.6 ml , 233 mmol) was added via syringe. The reaction was slowly warmed to rt and stirred overnight. The solvent was removed under reduced pressure, and the residue was diluted with AcOEt and aqueous NU4Cl (NH4Cl 7.2 g/200 ml water). The organic layer was separated, and the aqueous layer was extracted with AcOEt twice. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and chromatographed on silica gel eluting with 7.5% EtOAc/hexanes to give the title compound 15.2 g (96%).

Workup

  1. temperatureUpon cooling in a dry ice-acetone bath
  2. additionwas added via syringe
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with AcOEt and aqueous NU4Cl (NH4Cl 7.2 g/200 ml water)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with AcOEt twice
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed on silica gel eluting with 7.5% EtOAc/hexanes

Sources & evidence

ORD record
ord-bddf4d843dbe4f8f82f40179a879d55b
Source dataset
uspto-grants-2003_11
Patent number
US06645997B2

Reaction notes

Loading…