2,6-Lutidine → 6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-2-phosphono-hex-4-enoic Acid Methyl Ester

HRID 910564Notes

Reaction equation

HRID 910564 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH:4]([P:30]([O:34]C)([O:32]C)=[O:31])[CH2:5][C:6]([CH3:29])=[CH:7][CH2:8][C:9]1[C:10]([O:22]CC[Si](C)(C)C)=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21].C[Si](Br)(C)C.N1C(C)=CC=CC=1C>C(#N)C>[CH3:1][O:2][C:3](=[O:36])[CH:4]([P:30]([OH:34])([OH:32])=[O:31])[CH2:5][C:6]([CH3:29])=[CH:7][CH2:8][C:9]1[C:10]([OH:22])=[C:11]2[C:15](=[C:16]([CH3:20])[C:17]=1[O:18][CH3:19])[CH2:14][O:13][C:12]2=[O:21]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 765410362-(Dimethoxy-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

Product 1

HCID 670102886-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-2-phosphono-hex-4-enoic Acid Methyl EsterYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(dimethoxy-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 (30 mg, 0.055 mmol) in acetonitrile (2 mL) was added trimethylsilyl bromide (0.18 mL). After 10 minutes, 2,6-lutidine (0.16 mL) was added to the reaction at ambient temperature. The reaction was allowed to proceed for 16 hours before it was concentrated to dryness. The residue was resuspended in a solution of DMF: H2O (8:2, 1 mL) and purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 18 mg of the product as a white powder. 1H NMR (300 MHz, CD3OD) δ 1.81 (s, 3H), 2.16 (s, 3H), 2.40-2.49 (m, 1H), 2.63 (dt, 1H, J=6, 17 Hz), 3.07 (ddd, 1H, J=4, 12, 23 Hz), 3.38 (3, 2H, J=7 Hz), 3.52 (s, 3H), 3.77 (s, 3H), 5.25 (s, 2H), 5.28 (t, 1H, J=7 Hz) ppm; 31P (121.4 MHz, CDCl3) δ 19.5 ppm; MS (m/z) 415.2 [M+H]+, 437.2 [M+Na]+.

Workup

  1. waitto proceed for 16 hours before it
  2. concentrationwas concentrated to dryness
  3. custompurified by RP HPLC

Sources & evidence

ORD record
ord-f6f2f91414ee4fe092fd05058b6dc39a
Source dataset
uspto-grants-2011_09
Patent number
US08022083B2

Reaction notes

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