Dimethylformamide → HCID 68556769, compound

HRID 2382090Notes

Reaction equation

HRID 2382090 reaction equation
[H-].[Na+].[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[NH:6][CH:5]=1.C[N:18](C=O)C>>[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:14])[F:15])[CH:11]=2)[N:6]([NH2:18])[CH:5]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 44549958HCID 44549958, compound

Product 1

HCID 68556769HCID 68556769, compoundYield 52%

Conditions

Temperature
0 °C

Procedure

60% NaH (1.21 g, 30.2 mmol) is added to a stirred solution of 3-methyl-5-trifluoromethyl-1H-indole (400 mg, 2.01 mmol) in DMF (6 mL) at 0° C. in portions. The mixture is stirred at 0° C. for 1 h. HOSA (1.14 g, 10.0 mmol) is added in portions at 0° C. and the mixture is allowed to warm to rt over 2 h. The reaction is quenched with aqueous saturated ammonium chloride, extracted with extracted three times with DCM. The combined organic layer is dried (Na2SO4), filtered and concentrated. The residue is chromatographed through silica gel eluting with 0-40% EtOAc in heptane to afford 3-methyl-5-trifluoromethyl-indol-1-ylamine (223 mg, 52%). MS: 215 (M+H); 1H NMR (300 MHz, CDCl3): δ=7.84 (s, 1H), 7.48 (s, 2H), 7.04 (s, 1H), 4.77 (s, 2H), 2.34 (s, 3H).

Workup

  1. additionHOSA (1.14 g, 10.0 mmol) is added in portions at 0° C.
  2. temperatureto warm to rt over 2 h
  3. customThe reaction is quenched with aqueous saturated ammonium chloride
  4. extractionextracted
  5. extractionwith extracted three times with DCM
  6. dry with materialThe combined organic layer is dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is chromatographed through silica gel eluting with 0-40% EtOAc in heptane

Sources & evidence

ORD record
ord-8298464c34864bee9fb8c42bad62ee8f
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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