Ammonium Chloride → HCID 45486473, compound

HRID 1876913Notes

Reaction equation

HRID 1876913 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:28])([C@@H:14]([C:21]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)=[O:22])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1.[CH3:29][Mg]Br.[Cl-].[NH4+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][N:11]3[C:20]=2[CH:19]=[C:18]2[C@@:13]([CH3:28])([C@@H:14]([C@@:21]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)([OH:22])[CH3:29])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 25517Ammonium ChlorideHCID 46180621HCID 46180621, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 45486473HCID 45486473, compoundYield 49%

Procedure

To a stirred solution of the above ((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)(thiophen-2-yl)methanone was added methylmagnesium bromide solution (3 M in diethyl ether, 2 mL, 6 mmol) dropwise at −78° C. under argon. The reaction mixture was then stirred at RT for 2.5 hr before saturated aqueous ammonium chloride solution (6 mL) was added slowly with water bath cooling. The mixture was extracted with ethyl acetate (3×5 mL). The combined organic solutions were dried (Na2SO4) and concentrated. Silica gel flash chromatography (10-100% ethyl acetate in hexanes) gave (S)-1-((5aR,6S)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-(thiophen-2-yl)ethanol (58 mg, 0.14 mmol, 49% yield for steps (h)+(i)+(j)) as a solid.

Workup

  1. additionwas added slowly with water bath
  2. temperaturecooling
  3. extractionThe mixture was extracted with ethyl acetate (3×5 mL)
  4. dry with materialThe combined organic solutions were dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1dd96f881e8340c99ef598a1cbc17a9c
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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