Ammonium Chloride → 2-(Bis-(2,2,2-trifluoroethoxy)phosphoryl)-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic Acid Methyl Ester

HRID 272218

Reaction equation

HRID 272218 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][P:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])([O:7][CH2:8][C:9]([F:12])([F:11])[F:10])=[O:6].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:31][C:32]([CH3:55])=[CH:33][CH2:34][C:35]1[C:43]([O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])=[C:42]2[C:38]([CH2:39][O:40][C:41]2=[O:51])=[C:37]([CH3:52])[C:36]=1[O:53][CH3:54].[Cl-].[NH4+]>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:19])[CH:4]([P:5]([O:7][CH2:8][C:9]([F:12])([F:10])[F:11])([O:13][CH2:14][C:15]([F:18])([F:16])[F:17])=[O:6])[CH2:31][C:32]([CH3:55])=[CH:33][CH2:34][C:35]1[C:43]([O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:48])[CH3:49])=[C:42]2[C:38](=[C:37]([CH3:52])[C:36]=1[O:53][CH3:54])[CH2:39][O:40][C:41]2=[O:51]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 184894Nsc 634137HCID 2724254Sodium bis(trimethylsilyl)amideHCID 670106966-(4-bromo-3-methyl-but-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one

Product 1

HCID 866016102-(Bis-(2,2,2-trifluoroethoxy)phosphoryl)-6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic Acid Methyl EsterYield 48.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [bis-(2,2,2-trifluoro-ethoxy)-phosphoryl]-acetic acid methyl ester (186 μL, 0.88 mmol) in anhydrous THF (2 mL) was added a solution of 1N NaN(TMS)2 in THF (0.88 mL, 0.88 mmol). The solution was stirred at room temperature for 30 minutes, whereupon a solution of 6-(4-bromo-3-methyl-but-2-enyl)-5-methoxy-4-methyl-7-(2-trimethylsilanyl-ethoxy)-3H-isobenzofuran-1-one (98 mg, 0.22 mmol) in THF (1 mL) was added. The reaction mixture was stirred overnight when a precipitate was observed. The reaction mixture was worked up by addition of a saturated aqueous solution of ammonium chloride and extraction of the product with EtOAc. The organic extract was dried and the product was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 72 mg (48%) of the product as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.05 (s, 9H), 1.22 (t, 3H, J=7 Hz), 1.81 (s, 3H), 2.18 (s, 3H), 2.5-2.7 (m, 2H), 3.3 (ddd, 1H, J=4, 12, 23 Hz), 3.40 (d, 2H, J=7 Hz), 3.65 (s, 3H), 3.76 (s, 3H), 4.29-5.13 (m, 6H), 5.13 (s, 2H), 5.28 (t, 1H, J=7 Hz) ppm; MS (m/z) 701.2 [M+Na]+.

Workup

  1. additionwas added
  2. extractionThe organic extract
  3. customwas dried
  4. customthe product was purified by RP HPLC

Sources & evidence

ORD record
ord-bb9787a4281e40d9b3e929e9250aff57
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Linked notes

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