Ammonium Chloride → (3S,5R)-3-(4-(benzyloxy)but-2-enyl)-5-(4-fluorophenyl)dihydrofuran-2(3H)-one

HRID 1643287Notes

Reaction equation

HRID 1643287 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]2[O:22][C:21](=[O:23])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.I[CH2:25][CH:26]=[CH:27][CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[NH4+].[Cl-]>C1COCC1>[CH2:30]([O:29][CH2:28][CH:27]=[CH:26][CH2:25][C@H:20]1[CH2:19][C@H:18]([C:15]2[CH:14]=[CH:13][C:12]([F:11])=[CH:17][CH:16]=2)[O:22][C:21]1=[O:23])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 7020398(R)-5-(4-fluorophenyl)dihydrofuran-2(3H)-oneHCID 66755281(4-Iodo-but-2-enyloxymethyl)-benzene

Product 1

HCID 66754577(3S,5R)-3-(4-(benzyloxy)but-2-enyl)-5-(4-fluorophenyl)dihydrofuran-2(3H)-oneYield 63.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

To a solution of lithium bis(trimethylsilyl)amide (4.6 mL, 4.6 mmol, 1M in THF) in anhydrous 40 mL THF at −70° C. was slowly added over 15 minutes ((R)-5-(4-fluorophenyl)dihydrofuran-2(3H)-one (685 mg, 3.8 mmol) as a solution in 4 mL THF. After the reaction mixture was stirred for 30 min at −70° C. a pre-cooled solution of (4-Iodo-but-2-enyloxymethyl)-benzene (1.3 g, 4.6 mmol) in 4 mL of THF was slowly added. The resulting mixture was stirred at −70° C. for 1 h and the temperature was slowly raised to room temperature over a period of 2 h. The mixture was poured into 20 mL saturated NH4Cl and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (2×30 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography eluting with 0% to 50% ethyl acetate/hexane to give 827 mg of the title compound as a light yellow oil.

Workup

  1. additionwas slowly added
  2. temperaturethe temperature was slowly raised to room temperature over a period of 2 h
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with brine (2×30 mL)
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under reduced pressure
  7. customthe product isolated by Flash column chromatography
  8. washeluting with 0% to 50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-edc13a9f3a7a42ee9568ee1cc63c70a3
Source dataset
uspto-grants-2012_02
Patent number
US08119692B2

Reaction notes

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