Dimethylformamide → 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol
Reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][C:15]([CH3:18])([OH:17])[CH3:16].C[N:20](C=O)C>>[NH2:20][N:9]1[C:10]2[C:6](=[CH:5][C:4]([F:3])=[CH:12][CH:11]=2)[C:7]([CH2:13][CH2:14][C:15]([CH3:18])([OH:17])[CH3:16])=[CH:8]1Participants
Conditions
- Temperature
- 0 °C
Procedure
A suspension of NaH (8.1 g, 204 mmol, 60% in mineral oil) in DMF (100 mL) at 0° C. is treated with 4-(5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (3 g, 13.6 mmol) and stirred at 0° C. for 0.5 h. The mixture is treated with HOSA (7.7 g, 68 mmol) portion wise and warmed to rt over 2 h. The mixture is then poured over ice, filtered through a pad of Celite, and extracted with EtOAc (3×100 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by filtration through a short plug of silica gel to afford 4-(1-amino-5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol, which is used in the next step without further purification. MS: 237 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.30 (m, 1H), 7.22 (m, 1H), 6.98 (m, 2H), 4.71 (s, NH2, 2H), 2.75 (m, 2H), 1.86 (m, 2H), 1.31 (s, 6H).
Workup
- additionThe mixture is treated with HOSA (7.7 g, 68 mmol) portion wise
- temperaturewarmed to rt over 2 h
- additionThe mixture is then poured over ice
- filtrationfiltered through a pad of Celite
- extractionextracted with EtOAc (3×100 mL)
- dry with materialThe combined organic layer is dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- filtrationThe residue is purified by filtration through a short plug of silica gel
Sources & evidence
- ORD record
- ord-070c0434271c486baca24c458aba37cd
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258130B2
Reaction notes
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