Diisopropylethylamine → (3S,4S)-tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate

HRID 588469Notes

Reaction equation

HRID 588469 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([N+:13]([O-:15])=[O:14])=[C:5]2Cl.CCN(C(C)C)C(C)C.[NH2:26][C@H:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][C@@H:28]1[F:40].CCOC(C)=O.CCCCCC>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([N+:13]([O-:15])=[O:14])=[C:5]2[NH:26][C@H:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:29][C@@H:28]1[F:40]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 21226206Ethyl acetate hexaneHCID 536303506-Bromo-4-chloro-7-fluoro-3-nitroquinolineHCID 57415840tert-Butyl (3S,4S)-4-amino-3-fluoropiperidine-1-carboxylate

Product 1

HCID 117876247(3S,4S)-tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylateYield 972.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

6-Bromo-4-chloro-7-fluoro-3-nitroquinoline (17.5 g, 0.0057 mol) was taken in dry DMF (200 mL) under N2 atmosphere. DIPEA (14.8 g, 0.114 mol) and (3S,4S)-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate (12.5 g, 0.057 mol) in dry DMF (50 mL) was added sequentially at RT. The resulting mixture was stirred for overnight at RT. The reaction was monitored by TLC (30% EtOAc/Hexane), after completion of reaction, the reaction mixture poured into ice water and extracted with EtOAc (3×200 mL). The combined EtOAc layers were washed with brine solution and water, dried over sodium sulphate. The organic layer was evaporated under vacuum and the residue was purified by column chromatography on silica gel (10-50% EtOAc-Hexane) to afford the (3S,4S)-tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4-yl)amino)-3-fluoropiperidine-1-carboxylate, 1 (27 g, 956% yield). 1HNMR (CDCl3, 400 MHz): δ 9.37 (s, 1H) 8.83-8.81 (d, 1H) 8.48-8.46 (d, 1H) 7.74-7.71 (d, 1H), 4-58-4.40 (m, 2H), 4.19-4.12 (m, 2H), 2.95-2.87 (m, 2H) 2.27-2.23 (m, 1H) 1.79-1.66 (m, 1H), 1.47 (s, 9H); LCMS: 98.84%, (M+2) 488.7; HPLC: 99.47%.

Workup

  1. customafter completion of reaction
  2. extractionextracted with EtOAc (3×200 mL)
  3. washThe combined EtOAc layers were washed with brine solution and water
  4. dry with materialdried over sodium sulphate
  5. customThe organic layer was evaporated under vacuum
  6. customthe residue was purified by column chromatography on silica gel (10-50% EtOAc-Hexane)

Sources & evidence

ORD record
ord-d0b6bc9aac2648719c645693eef10e5d
Source dataset
uspto-grants-2016_01
Patent number
US09227969B2

Reaction notes

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