Ammonium Chloride → 2-[(1RS,2SR)-1-hydroxy-2-[(3-methoxyphenyl)methyl]cyclohexyl]-4,5-diphenyloxazole

HRID 377302Notes

Reaction equation

HRID 377302 reaction equation
O1CCCC1.C([N-]C(C)C)(C)C.[Li+].[C:14]1([C:20]2[N:21]=[CH:22][O:23][C:24]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH2:39][CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][C:41]2=[O:46])[CH:36]=[CH:37][CH:38]=1.[Cl-].[NH4+]>C1CCCCC1.O1CCCC1.C(OCC)C.C(Cl)(Cl)(Cl)Cl>[OH:46][C:41]1([C:22]2[O:23][C:24]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[C:20]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:21]=2)[CH2:42][CH2:43][CH2:44][CH2:45][CH:40]1[CH2:39][C:35]1[CH:36]=[CH:37][CH:38]=[C:33]([O:32][CH3:31])[CH:34]=1

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 6134984,5-DiphenyloxazoleHCID 10997623Lithium diisopropylamide mono(tetrahydrofuran)HCID 148680162-(3-Methoxy-benzyl)-cyclohexanone

Product 1

HCID 184591732-[(1RS,2SR)-1-hydroxy-2-[(3-methoxyphenyl)methyl]cyclohexyl]-4,5-diphenyloxazoleYield 37.6%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Procedure

A 1.5 M solution of lithium diisopropylamide mono(tetrahydrofuran) in cyclohexane (19.9 ml) was added dropwise to a stirred solution of 4,5-diphenyloxazole (6.0 g) in tetrahydrofuran (36 ml) and diethyl ether (18 ml) under dry ice--carbon tetrachloride cooling and the mixture was stirred at the same temperature for a while and at 0° C. for a while. A solution of 2-[(3-methoxyphenyl)methyl]cyclohexanone (5.92 g) in tetrahydrofuran (16 ml) was added to the reaction mixture under dry ice-acetone cooling, and the resulting mixture was stirred at the same temperature for several hours. Then the reaction temperature was allowed to rise gradually to room temperature and the reaction mixture was allowed to stand at room temperature overnight. The mixture was treated with ammonium chloride aqueous solution and partitioned between ethyl acetate and 1N hydrochloric acid. The ethyl acetate layer was separated and washed successively with 1N hydrochloric acid (twice), sodium bicarbonate aqueous solution, and brine, dried over magnesium sulfate, and evaporated in vacuo. The oily residue was chromatographed (n-hexane - ethyl acetate (10:1)) over silica gel. The first eluate afforded 2-[(1RS,2RS)-1-hydroxy-2-[(3-methoxyphenyl)methyl]-cyclohexyl]-4,5-diphenyloxazole (4.48 g) as pale yellow paste.

Workup

  1. customto rise gradually to room temperature
  2. custompartitioned between ethyl acetate and 1N hydrochloric acid
  3. customThe ethyl acetate layer was separated
  4. washwashed successively with 1N hydrochloric acid (twice), sodium bicarbonate aqueous solution, and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe oily residue was chromatographed (n-hexane - ethyl acetate (10:1)) over silica gel

Sources & evidence

ORD record
ord-aba60a4d061d43c2988a38106c09ab94
Source dataset
uspto-grants-2000_02
Patent number
US06025375

Reaction notes

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