Trifluoroacetic acid → 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)acetic acid

HRID 1876920Notes

Reaction equation

HRID 1876920 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]([CH3:26])([C@@H:14]([CH2:21][CH:22]([O:24]C)[OH:23])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1.CC(=CC)C.FC(F)(F)C(O)=O.Cl([O-])=O.[Na+].O.P([O-])(O)(O)=O.[Na+]>O.C(O)(C)(C)C>[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]([CH3:26])([C@@H:14]([CH2:21][C:22]([OH:24])=[O:23])[CH2:15][CH2:16][CH2:17]2)[CH2:12]3)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 584817592-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol

Product 1

HCID 584817822-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)acetic acidYield 229.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a stirred mixture of 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)-1-methoxyethanol (Example 5a, 90 mg, 0.25 mmol), 2-methylbut-2-ene (2 M in THF, 1 mL), tert-butanol (0.5 mL) and trifluoroacetic acid (0.03 mL, 0.4 mmol) was added a solution of sodium chlorite (80%, 70 mg, 0.62 mmol) and sodium dihydrogenphosphate monohydrate (80 mg, 0.58 mmol) in water (0.6 mL) at 0° C. The reaction mixture was then stirred at RT for 1.5 hr. The aqueous layer was separated, extracted with THF (1.5 mL), neutralized with solid sodium bicarbonate to pH=6, and extracted with THF (2×1 mL). The combined organic solutions were dried (Na2SO4) and concentrated to give 2-((5aR,6R)-1-(4-fluorophenyl)-5a-methyl-5,5a,6,7,8,9-hexahydroimidazo[1,5-b]isoquinolin-6-yl)acetic acid (195 mg) which was used in the next step without further purification. MS found: (M+H)+=341.2.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with THF (1.5 mL)
  3. extractionextracted with THF (2×1 mL)
  4. dry with materialThe combined organic solutions were dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3426985a315f45e3bd48310eba2e997c
Source dataset
uspto-grants-2012_11
Patent number
US08309730B2

Reaction notes

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