2,6-Lutidine → 2-[4-(Dihydroxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic Acid

HRID 33622

Reaction equation

HRID 33622 reaction equation
C[O:2][P:3]([CH2:7][CH:8]=[CH:9][CH2:10][CH:11]([CH2:15][C:16]([CH3:33])=[CH:17][CH2:18][C:19]1[C:20]([OH:32])=[C:21]2[C:25](=[C:26]([CH3:30])[C:27]=1[O:28][CH3:29])[CH2:24][O:23][C:22]2=[O:31])[C:12]([OH:14])=[O:13])([O:5]C)=[O:4].N1C(C)=CC=CC=1C.C[Si](Br)(C)C>C(#N)C>[OH:5][P:3]([CH2:7][CH:8]=[CH:9][CH2:10][CH:11]([CH2:15][C:16]([CH3:33])=[CH:17][CH2:18][C:19]1[C:20]([OH:32])=[C:21]2[C:25](=[C:26]([CH3:30])[C:27]=1[O:28][CH3:29])[CH2:24][O:23][C:22]2=[O:31])[C:12]([OH:14])=[O:13])([OH:4])=[O:2]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 765461892-[4-(Dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic Acid

Product 1

HCID 725636302-[4-(Dihydroxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic AcidYield 60.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-[4-(dimethoxy-phosphoryl)-but-2-enyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoic acid (25 mg, 0.052 mmol) in acetonitrile (2 mL) was added 2,6-lutidine (60 μL, 0.52 mmol) and TMSBr (67 μL, 0.52 mmol). The reaction was allowed to proceed for 45 minutes when it was completed as judged by LCMS. The reaction mixture was concentrated under reduced pressure and quenched with an aqueous NaOH solution (1 mL). 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 14.2 mg (60%) of the product as a solid. 1H NMR (300 MHz, CD3OD) δ 1.81 (s, 3H), 2.081-2.31 (m, 4H), 2.16 (s, 3H), 2.45 (d, 1H, J=22 Hz), 2.47 (d, 1H, J=22 Hz), 2.55-2.63 (m, 1H), 3.38 (d, 2H, J=7 Hz), 3.77 (s, 3H), 5.25 (s, 2H), 5.20-5.36 (m, 1H), 5.36-5.56 (m, 2H) ppm; 31P (121.4 MHz, CD3OD) δ 25.4 ppm; MS (m/z) 453 [M−H]−.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customquenched with an aqueous NaOH solution (1 mL)
  3. customThe product was purified by RP HPLC (

Sources & evidence

ORD record
ord-c23cf22309fa40839bbe60b655517eb1
Source dataset
uspto-grants-2008_09
Patent number
US07429565B2

Linked notes

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