Tert-Butylamine → N-tert-butyl-4-(difluoromethyl)pyridin-2-amine
Reaction equation
[F:1][CH:2]([F:10])[C:3]1[CH:8]=[CH:7][N+:6]([O-])=[CH:5][CH:4]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)CC)C.[C:42]([NH2:46])([CH3:45])([CH3:44])[CH3:43]>ClCCCl.C(Cl)Cl>[C:42]([NH:46][C:7]1[CH:8]=[C:3]([CH:2]([F:10])[F:1])[CH:4]=[CH:5][N:6]=1)([CH3:45])([CH3:44])[CH3:43]Participants
Conditions
- Temperature
- 100 °C
Procedure
A suspension of 4-difluoromethyl-pyridine-N-oxide (4.95 g, 34.1 mmol), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (20.7 g, 44.3 mmol), triethylamine (15.6 mL, 111 mmol), and anhydrous tert-butylamine (4.6 mL, 43 mmol) in DCE (100 mL, 0.33 M) was sealed in pressure tube and stirred at 100° C. for 3.5 hr. After cooling to rt, the mixture was diluted with CH2Cl2 and washed with sat. aq. NaHCO3. The organics were dried over MgSO4 and following concentration, the reaction residue was purified by flash column chromatography (100:0-80:20 heptanes/EtOAc) to afford N-tert-butyl-4-(difluoromethyl)pyridin-2-amine as a yellow liquid (4.43 g, 65%); 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=5.2 Hz, 1H), 6.65-6.28 (m, 3H), 4.62 (br s, 1H), 1.44 (s, 9H).
Workup
- customwas sealed in pressure tube
- temperatureAfter cooling to rt
- washwashed with sat. aq. NaHCO3
- dry with materialThe organics were dried over MgSO4
- concentrationconcentration
- customthe reaction residue was purified by flash column chromatography (100:0-80:20 heptanes/EtOAc)
Sources & evidence
- ORD record
- ord-a2a0f222d2ad4652b9f30c5e94e21303
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09399636B2
Reaction notes
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