Benzophenone → Hexahydro-1,1-diphenyl-7-(phenylmethyl)-3H-oxazolo[3,4-a]pyrazin-3-one

HRID 1713484Notes

Reaction equation

HRID 1713484 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=[O:15])[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)CCN(C)C.C([Li])(CC)C.C1CCCCC1.[C:40]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)(=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:41]1([C:40]2([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[CH:10]3[CH2:9][N:8]([CH2:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:13][CH2:12][N:11]3[C:14](=[O:15])[O:47]2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 6

HCID 3102BenzophenoneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8078CyclohexaneHCID 25517Ammonium ChlorideHCID 584330Tert-butyl 4-benzylpiperazine-1-carboxylateHCID 178418400CID 53628100

Product 1

HCID 23121969Hexahydro-1,1-diphenyl-7-(phenylmethyl)-3H-oxazolo[3,4-a]pyrazin-3-oneYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

1,1-Dimethylethyl 4-(phenylmethyl)-1-piperazine carboxylate (20 g, 72 mmol) and tetramethylethylenediamine (18 g, 0.16 mol) were dissolved in tetrahydrofuran (100 mL), and the solution was cooled to −78° C. A 1.0 M solution of sec-butyllithium in hexane and cyclohexane (150 mL, 0.15 mol) was added thereto, and the mixture was stirred for 2 hours and the temperature was elevated to −30° C. After cooling to −78° C. again, a solution of benzophenone (28 g, 0.15 mol) in tetrahydrofuran (70 mL) was added dropwise thereto, and the mixture was stirred for 18 hours while elevating the temperature to room temperature. To the reaction solution was added an aqueous saturated ammonium chloride solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain the title compound (18 g, yield 64%) as crystals.

Workup

  1. customwas elevated to −30° C
  2. temperatureAfter cooling to −78° C. again
  3. stirringthe mixture was stirred for 18 hours
  4. customto room temperature
  5. extractionthe resulting mixture was extracted with ethyl acetate
  6. washThe extract was washed with water
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified with silica gel column chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-408d58ba17d24275998c09d452a612d8
Source dataset
uspto-grants-2010_09
Patent number
US07795267B2

Reaction notes

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