Hexamethylphosphoramide → Ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-2-propylchromane-2-carboxylate

HRID 479633Notes

Reaction equation

HRID 479633 reaction equation
[CH2:1]([C:4]1[CH:29]=[C:28]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:27]=[CH:26][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][CH2:16][CH:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[O:18]2)=[CH:13][CH:12]=1)[CH2:2][CH3:3].CN(C)P(N(C)C)(N(C)C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].I[CH2:59][CH2:60][CH3:61]>C1COCC1>[CH2:1]([C:4]1[CH:29]=[C:28]([O:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:27]=[CH:26][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][CH2:16][C:17]([CH2:59][CH2:60][CH3:61])([C:21]([O:23][CH2:24][CH3:25])=[O:22])[O:18]2)=[CH:13][CH:12]=1)[CH2:2][CH3:3]

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 336431-IodopropaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 18772266Ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-chromane-2-carboxylate

Product 1

HCID 18772268Ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-2-propylchromane-2-carboxylateYield 30.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 2 ml THF solution of ethyl 7-(3-(2-propyl-4-phenoxyphenoxy)propoxy)-chromane-2-carboxylate (Example 1, Step B) (100 mg, 0.204 mmol) were added hexamethylphosphoramide (0.046 ml, 0.26 mmol) and sodium bis(trimethylsilyl)amide (1.0M THF solution) (0.265 ml, 0.265 mmol) upon cooling in a dry ice-acetone bath. After stirring at that temperature for 30min, to it was added iodopropane (0.06 ml, 6.2 mmol). The cooling bath was removed and the reaction mixture was gradually warmed to rt overnight. The solvent was removed under reduced pressure, diluted with AcOEt and water. The organic layer was separated. The aqueous layer was extracted twice with AcOEt. The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated, and chromatographed on silica gel. Elution with 5% AcOEt/hexanes gave the title compound as a clear oil 33 mg (30%).

Workup

  1. temperatureupon cooling in a dry ice-acetone bath
  2. customThe cooling bath was removed
  3. customThe solvent was removed under reduced pressure
  4. additiondiluted with AcOEt and water
  5. customThe organic layer was separated
  6. extractionThe aqueous layer was extracted twice with AcOEt
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed on silica gel
  11. washElution with 5% AcOEt/hexanes

Sources & evidence

ORD record
ord-064633f716e8441997a81df662da6c89
Source dataset
uspto-grants-2003_11
Patent number
US06645997B2

Reaction notes

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