Ammonium Chloride → HCID 18546280, compound

HRID 1267768Notes

Reaction equation

HRID 1267768 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:11][O:12][CH2:13][O:14][C:15]1[CH:24]=[C:23]2[C:18]([CH:19]([CH2:36][CH:37]=[CH2:38])[CH:20]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][O:34][CH3:35])=[CH:28][CH:27]=3)[C:21](=[O:25])[O:22]2)=[CH:17][CH:16]=1.O([CH2:47][CH3:48])S(C(F)(F)F)(=O)=O.[Cl-].[NH4+]>O1CCCC1.O.N1C=CC=CC=1>[CH2:47]([C:20]1([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][O:34][CH3:35])=[CH:28][CH:27]=2)[CH:19]([CH2:36][CH:37]=[CH2:38])[C:18]2[C:23](=[CH:24][C:15]([O:14][CH2:13][O:12][CH3:11])=[CH:16][CH:17]=2)[O:22][C:21]1=[O:25])[CH3:48]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 67924Ethyl trifluoromethanesulphonateHCID 2733832Lithium HexamethyldisilazideHCID 18546282HCID 18546282, compound

Product 1

HCID 18546280HCID 18546280, compoundYield 84.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 1M solution of lithium hexamethyl-disilazide in tetrahydrofuran (86.2 ml) was added dropwise to a solution of 7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-4-(2-propenyl)chroman-2-one (16.57 g) in dry tetrahydrofuran (86.2 ml) at −78° C. over 30 minutes under nitrogen atmosphere, followed by stirring for 20 minutes at 0° C. After the reaction mixture was cooled to −78° C., ethyl triflate (21.6 ml) was added dropwise thereto over 20 minutes and the resulting mixture was warmed to −30° C. over 3 hours, followed by addition of pyridine (13.9 ml). This mixture was stirred for 15 minutes at −30° C., cooled to −78° C., and further mixed with saturated aqueous ammonium chloride (100 ml) and water (50 ml). After extraction with ethyl acetate, the organic layer was washed with 0.05 N aqueous hydrochloric acid and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate. After concentration under reduced pressure, the resulting oil was purified by flash column chromatography (silica gel: Merck Kieselgel 60, eluent: hexane/ethyl acetate=5/1→4/1) to give (3RS,4RS)-3-ethyl-7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-4-(2-propenyl)chroman-2-one (14.98 g, Yield 84.3%) as a white solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to −78° C.
  2. waitover 20 minutes
  3. temperaturethe resulting mixture was warmed to −30° C. over 3 hours
  4. stirringThis mixture was stirred for 15 minutes at −30° C.
  5. temperaturecooled to −78° C.
  6. extractionAfter extraction with ethyl acetate
  7. washthe organic layer was washed with 0.05 N aqueous hydrochloric acid and saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationAfter concentration under reduced pressure
  10. customthe resulting oil was purified by flash column chromatography (silica gel: Merck Kieselgel 60, eluent: hexane/ethyl acetate=5/1→4/1)

Sources & evidence

ORD record
ord-85dd1244652245f6b00de83e286afc67
Source dataset
uspto-grants-2003_04
Patent number
US06552068B1

Reaction notes

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