Tetrahydrofuran → HCID 22263187, compound

HRID 489918Notes

Reaction equation

HRID 489918 reaction equation
C(N(CC)[C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([C:20]3[C:21]4[C:26]([CH:27]=[C:28]5[C:33]=3[CH:32]=[CH:31][CH:30]=[CH:29]5)=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:19])[CH2:14][CH2:13]2)[CH2:7]1)=[O:5])C.[CH2:36]([Mg]Br)[CH3:37].O1CC[CH2:42][CH2:41]1>>[CH:22]1[C:21]2[C:26](=[CH:27][C:28]3[C:33]([C:20]=2[C:18]([N:15]2[CH2:16][CH2:17][CH:12]([N:8]4[CH2:9][CH2:10][CH2:11][CH:6]([C:4]([CH2:36][CH3:37])([OH:5])[CH2:41][CH3:42])[CH2:7]4)[CH2:13][CH2:14]2)=[O:19])=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 9804834HCID 9804834, compound2×HCID 178418443HCID 178418443, compound2×

Product 1

HCID 22263187HCID 22263187, compoundYield 15%

Procedure

To a solution of (3R)-1′-(anthracene-9-carbonyl)-[1,4′]bipiperidinyl-3-carboxylic acid diethylamide (Intermediate 22, 22.2 mg, 47 μmol) in anhydrous tetrahydrofuran (0.5 mL) under nitrogen at −25° C. was added a solution of ethylmagnesium bromide (1M in tetrahydrofuran, 2.1 eq., 0.1 mL). The solution was allowed to warm to ambient temperature and after 30 min a further addition of ethylmagnesium bromide (1M in tetrahydrofuran, 4.2 eq., 0.2 mL) was made. The mixture was stirred for 16 hr at ambient temperature before quenching with methanol. The mixture was diluted with dichloromethane, washed with a mixture of sodium hydroxide and sodium hydrogen carbonate solutions, dried over anhydrous sodium sulfate and the solvent was removed by evaporation under vacuum. The crude product was purified by chromatography on silica gel eluting with a 1%-10% methanol-dichloromethane gradient to give the title compound (3.2 mg, 15%).

Workup

  1. custombefore quenching with methanol
  2. additionThe mixture was diluted with dichloromethane
  3. washwashed with a mixture of sodium hydroxide and sodium hydrogen carbonate solutions
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed by evaporation under vacuum
  6. customThe crude product was purified by chromatography on silica gel eluting with a 1%-10% methanol-dichloromethane gradient

Sources & evidence

ORD record
ord-348fc969e61745a5b3d08bd392630d73
Source dataset
uspto-grants-2005_12
Patent number
US06979741B2

Reaction notes

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