2,2,6,6-Tetramethylpiperidine → 3-(Diphenyl-phosphinoyl)-6-methoxy-2-(4-methoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 1761019Notes

Reaction equation

HRID 1761019 reaction equation
C[C:2]1([CH3:10])[CH2:7][CH2:6][CH2:5][C:4](C)(C)N1.C1([C:17](C2C=CC=CC=2)([PH2:39]=[O:40])[N:18]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:19](=[O:29])[C:20]2[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:21]=2F)C=CC=CC=1>C1COCC1.[Cl-].[NH4+]>[C:6]1([P:39]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:2][CH:10]=2)([CH:17]2[C:21]3[C:20](=[CH:25][C:24]([O:26][CH3:27])=[CH:23][CH:22]=3)[C:19](=[O:29])[N:18]2[CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)=[O:40])[CH:5]=[CH:4][CH:10]=[CH:2][CH:7]=1

Participants

5

Reactant 2

HCID 130352,2,6,6-TetramethylpiperidineHCID 178491163HCID 178491163, compound

Product 1

HCID 225942173-(Diphenyl-phosphinoyl)-6-methoxy-2-(4-methoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 41%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a cooled solution (−78° C.) of 2,2,6,6-tetramethylpiperidine (5.7 g, 40.3 mmol) in THF (60 mL) BuLi (25 mL, 1.6 M in hexanes, 40.3 mmol) was added. To the resulting mixture a solution of N-(diphenyl-phosphinoylmethyl)-2-fluoro-5-methoxy-N-(4-methoxy-benzyl)-benzamide (9.2 g, 18.3 mmol) in THF (55 mL) was added at such a rate to maintain the temperature below −70° C. and maintained at this temperature for 30 min. The reaction mixture was then allowed to warm up to RT over 5 h, and diluted with ammonium chloride (200 mL). The product was then extracted with diethyl ether and the combined extracts washed with brine. The residue was then evaporated and purified by chromatography (SiO2, Hexane:Acetone 1:1) to afford the title product (3.6 g, 41%) as a light yellow solid. MS m/e=484.3 (M+H+).

Workup

  1. temperatureto maintain the temperature below −70° C.
  2. temperaturemaintained at this temperature for 30 min
  3. extractionThe product was then extracted with diethyl ether
  4. washthe combined extracts washed with brine
  5. customThe residue was then evaporated
  6. custompurified by chromatography (SiO2, Hexane:Acetone 1:1)

Sources & evidence

ORD record
ord-5b8646046e12438bb31bec7fce185f27
Source dataset
uspto-grants-2005_01
Patent number
US06846832B2

Reaction notes

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