4-Fluoroaniline → HCID 71008326, compound

HRID 1887487Notes

Reaction equation

HRID 1887487 reaction equation
Br[CH:2]([CH:6]([CH3:8])[CH3:7])[C:3](O)=[O:4].O=S(Cl)Cl.[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1.[F:21][C:22]([F:42])([F:41])[CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][CH:34]3[CH2:37][NH:38][CH2:39][CH:33]3[C:32]2=[O:40])=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C=O)C.O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:3](=[O:4])[CH:2]([N:38]2[CH2:37][CH:34]3[CH:33]([C:32](=[O:40])[N:31]([C:28]4[CH:29]=[CH:30][C:25]([O:24][CH2:23][C:22]([F:21])([F:41])[F:42])=[CH:26][CH:27]=4)[CH2:36][CH2:35]3)[CH2:39]2)[CH:6]([CH3:8])[CH3:7])=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 97314-FluoroanilineHCID 112682-Bromoisovaleric acidHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 71008531HCID 71008531, compound

Product 1

HCID 71008326HCID 71008326, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2-Bromo-3-methylbutanoic acid (2.5 g, 14 mmol) was added to 20 mL of SOCl2. The mixture was refluxed for 1 h. The superfluous SOCl2 was removed. The residue was added into the solution of 4-fluorobenzenamine (1.33 g, 12 mmol) in 10 mL of DCM. The mixture was stirred at ambient temperature for 0.5 h and evaporated to dryness. The crude product (3.0 g, 78%) was used in the subsequent step without further purification. A mixture of 5-[4-(2,2,2-Trifluoro-ethoxy)-phenyl]-octahydro-pyrrolo[3,4-c]pyridin-4-one (90 mg, 26 mmol), the crude α-bromoamide (211 mg, 0.77 mmol) and K2CO3 (106 mg, 0.77 mmol) in 15 mL of DMF was heated to 85° C. overnight. The mixture was diluted with water (15 mL) and extracted with EtOAc (2×20 mL), the combined organic layers was washed with water (2×10 mL), brine (2×10 mL), dried with anhydrous Na2SO4 and evaporated to dryness. The residue was purified with prep-TLC (eluting with DCM/MeOH=30:1) to obtain the title compound (33 mg, 25%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.29-7.13 (m, 2H), 7.01-6.84 (m, 4H), 6.69-6.65 (m, 2H), 6.61 (bs, 1H), 4.43-4.35 (m, 2H), 4.03-3.65 (m, 7H), 3.29-3.27 (m, 1H), 2.80 (bs, 1H), 2.10-1.65 (m, 3H), 1.11-1.07 (t, 6H, J=5.4 Hz). LC-MS: 508.2 [M+1]+.

Workup

  1. temperatureThe mixture was refluxed for 1 h
  2. customThe superfluous SOCl2 was removed
  3. customevaporated to dryness
  4. customThe crude product (3.0 g, 78%) was used in the subsequent step without further purification
  5. extractionextracted with EtOAc (2×20 mL)
  6. washthe combined organic layers was washed with water (2×10 mL), brine (2×10 mL)
  7. dry with materialdried with anhydrous Na2SO4
  8. customevaporated to dryness
  9. customThe residue was purified with prep-TLC (eluting with DCM/MeOH=30:1)

Sources & evidence

ORD record
ord-814cabfd7061453a9e1e788ef8dd5e8a
Source dataset
uspto-grants-2013_08
Patent number
US08501768B2

Reaction notes

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