Ammonium Chloride → {1-Cyano-3-ethyl-5-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-pent-3-enyl}-phosphonic Acid Diethyl Ester

HRID 32996

Reaction equation

HRID 32996 reaction equation
[C:1]([CH2:3][P:4](=[O:11])([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])#[N:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:23][C:24]([CH2:47][CH3:48])=[CH:25][CH2:26][C:27]1[C:35]([O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])=[C:34]2[C:30]([CH2:31][O:32][C:33]2=[O:43])=[C:29]([CH3:44])[C:28]=1[O:45][CH3:46].[Cl-].[NH4+]>C1COCC1>[CH2:6]([O:5][P:4]([CH:3]([C:1]#[N:2])[CH2:23][C:24]([CH2:47][CH3:48])=[CH:25][CH2:26][C:27]1[C:35]([O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:40])[CH3:41])=[C:34]2[C:30](=[C:29]([CH3:44])[C:28]=1[O:45][CH3:46])[CH2:31][O:32][C:33]2=[O:43])(=[O:11])[O:8][CH2:9][CH3:10])[CH3:7]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 670098846-(3-Bromomethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one

Product 1

HCID 72563633{1-Cyano-3-ethyl-5-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-pent-3-enyl}-phosphonic Acid Diethyl EsterYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diethyl cyanomethylphosphonate (233 mg, 1.32 mmol) in THF (1 mL) was added a THF solution of sodium bis(trimethysilyl)amide (1.0 M, 1.21 mL, 1.21 mmol). After stirring for 30 minutes, the solution was added dropwise to a solution of 6-(3-bromomethyl-pent-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one (100 mg, 0.22 mmol) in THF (1 mL). The resulting mixture was allowed to stir at room temperature overnight before saturated aqueous ammonium chloride was added. The reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to dryness. The residue was purified by preparative reverse-phase HPLC, affording 51 mg (42%) of the desired product.

Workup

  1. additionwas added
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-a3c4a8898c274e60bd1c052aebb25603
Source dataset
uspto-grants-2008_09
Patent number
US07427636B2

Linked notes

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