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

HRID 910147Notes

Reaction equation

HRID 910147 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[F: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:15][C:3]1[C:4](=[O:14])[N:5]2[C:9](=[C:10]([C:11]([OH:13])=[O:12])[C:2]=1[NH:19][C:18]1[CH:20]=[CH:21][C:22]([I:24])=[CH:23][C:17]=1[F:16])[CH2:8][CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 576898127-Chloro-6-fluoro-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid

Product 1

HCID 252657696-Fluoro-7-(2-fluoro-4-iodophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acidYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 1d (240 mg, 1.04 mmol) and 2-fluoro-4-iodoaniline (493 mg, 2.08 mmol) stirred in dry THF (10 ml) at 0° C. under nitrogen. LiHMDS (1M in THF, 3.11 mL, 3.11 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 16% MeOH/CH2Cl2) gave 238 mg (53%) of Example 1 as a tan solid. 1H NMR (400 MHz, MeOD-d4): δ 7.22-7.31 (m, 2H), 6.67 (t, 1H, J=8.0 Hz), 4.06 (t, 2H, J=7.6 Hz), 3.45 (t, 2H, J=7.6 Hz), 2.05-2.15 (m, 2H). MS (ES) [m+H] calc'd for C15H11F2IN2O3, 433. found 433.

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 16% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ae72d3f411a8460781ea829d9f7b6f5e
Source dataset
uspto-grants-2011_09
Patent number
US08022057B2

Reaction notes

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