2-Fluoro-4-iodoaniline → 7-(2-Fluoro-4-iodophenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid

HRID 910159Notes

Reaction equation

HRID 910159 reaction equation
Cl[C:2]1[C:10]([C:11]([OH:13])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:14])[C:3]=1[CH3:15].[F:16][C:17]1[CH:23]=[C:22]([I:24])[CH:21]=[CH:20][C:18]=1[NH2:19].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:16][C:17]1[CH:23]=[C:22]([I:24])[CH:21]=[CH:20][C:18]=1[NH:19][C:2]1[C:10]([C:11]([OH:13])=[O:12])=[C:9]2[N:5]([CH2:6][CH2:7][CH2:8]2)[C:4](=[O:14])[C:3]=1[CH3:15]

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 576898047-Chloro-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid

Product 1

HCID 576898057-(2-Fluoro-4-iodophenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acidYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 8d (183 mg, 1.04 mmol) and 2-fluoro-4-iodoaniline (384 mg, 1.62 mmol) stirred in dry THF (8 ml) at 0° C. under nitrogen. LiHMDS (1M in THF, 2.4 mL, 2.4 mmol) was added dropwise, and the reaction stirred 4 h while warming to RT. The solution was quenched with 1N HCl and extracted with 10% MeOH/CH2Cl2 (3×). Organics were dried (MgSO4) and concentrated in vacuo. Purification by silica gel chromatography (10% to 20% MeOH/CH2Cl2) gave 76 mg (22%) of compound 8e as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ7.57 (d, 1H, J=9.1 Hz), 7.37 (d, 1H, J=8.3 Hz), 6.38 (t, 1H, J=9.0 Hz), 4.00 (t, 2H, J=7.6 Hz), 3.41 (t, 2H, J=8.1 Hz), 2.06-2.09 (m, 2H), 1.61 (s, 3H). MS (ES) [m+H] calc'd for C16H14FIN2O3, 429. found 429.

Workup

  1. customThe solution was quenched with 1N HCl
  2. extractionextracted with 10% MeOH/CH2Cl2 (3×)
  3. dry with materialOrganics were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by silica gel chromatography (10% to 20% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-2ec2b360a38147b6938babac4394fa82
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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