2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → HCID 67490991, compound

HRID 1917419Notes

Reaction equation

HRID 1917419 reaction equation
[C:1]([O:5][C:6]([C@H:8]1[C@H:12]([C:13]([CH2:15]Br)=[CH2:14])[CH2:11][N:10]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCCN(C)C1=O.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>O1CCCC1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([C@@:8]12[CH2:14][C:13](=[CH2:15])[C@@H:12]1[CH2:11][N:10]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[CH2:9]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2733832Lithium HexamethyldisilazideHCID 67491102HCID 67491102, compound

Product 1

HCID 67490991HCID 67490991, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(3S,4R)-1-Benzyloxycarbonyl-4-[1-(bromomethyl)vinyl]pyrrolidine-3-carboxylic acid tert-butyl ester (22.8 g, 53.7 mmol) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (19.5 mL, 161 mmol) were dissolved in a mixed solution of tetrahydrofuran (220 mL) and toluene (220 mL). Lithium hexamethyldisilazide (1.0 M solution in tetrahydrofuran) (80.6 mL, 80.6 mmol) was added dropwise at −78° C., and then the mixture was stirred at room temperature for five minutes. The reaction solution was extracted with a saturated ammonium chloride solution and ethyl acetate. Then, the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:ethyl acetate=24:1→2:1) to give 8.34 g of the title compound as a colorless syrup.

Workup

  1. extractionThe reaction solution was extracted with a saturated ammonium chloride solution and ethyl acetate
  2. washThen, the organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bc4748bbfc1b4de98063d3f36b32ea70
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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