Ammonium formate → (R)-3-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol

HRID 1964478Notes

Reaction equation

HRID 1964478 reaction equation
[CH3:1][C:2]1([CH3:27])[O:6][C@H:5]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([N+:18]([O-])=O)=[C:14]([F:17])[CH:15]=3)[CH:10]=[C:9]2[C:21]([CH3:26])([CH3:25])[CH2:22][CH2:23][OH:24])[CH2:4][O:3]1.FC1C=C2C(C=C(C(C)(C)CCO)N2)=CC=1[N+]([O-])=O.C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:18][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][C:14]=1[F:17])[N:8]([CH2:7][C@@H:5]1[CH2:4][O:3][C:2]([CH3:1])([CH3:27])[O:6]1)[C:9]([C:21]([CH3:26])([CH3:25])[CH2:22][CH2:23][OH:24])=[CH:10]2

Participants

6

Reactant 3

HCID 2723923Ammonium formateHCID 59129188(R)-3-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-olHCID 591293673-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol

Product 1

HCID 58201776(R)-3-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of (R)-3-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol containing some 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol (500 mg, 1.3 mmol) in ethanol (10 mL) was added ammonium formate (500 mg, 7.9 mmol) and Pd/C (10%, 139 mg, 0.13 mmol). The mixture was refluxed for 5 min. The Pd catalyst was removed via filtration through Celite and washed with ethanol. The filtrate was evaporated to dryness and purified by column chromatography (30-50% ethyl acetate-hexanes) to provide (R)-3-(5-amino-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol (220 mg, 48%, contains some 3-(5-amino-6-fluoro-1H-indol-2-yl)-3-methylbutan-1-ol). ESI-MS m/z calc. 350.2 found 351.4 (M+1)+. Retention time 0.94 minutes.

Workup

  1. temperatureThe mixture was refluxed for 5 min
  2. customThe Pd catalyst was removed via filtration through Celite
  3. washwashed with ethanol
  4. customThe filtrate was evaporated to dryness
  5. custompurified by column chromatography (30-50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-a415a9384fe44da9a5b33dbf0586cd4c
Source dataset
uspto-grants-2013_04
Patent number
US08415387B2

Reaction notes

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