2,6-Lutidine → HCID 67011361, compound

HRID 2281989Notes

Reaction equation

HRID 2281989 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][C:11]([CH3:34])=[CH:12][CH2:13][C:14]1[C:15]([O:27]CC[Si](C)(C)C)=[C:16]2[C:20](=[C:21]([CH3:25])[C:22]=1[O:23][CH3:24])[CH2:19][O:18][C:17]2=[O:26])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>CN(C=O)C.C(Cl)Cl>[OH:27][C:15]1[C:14]([CH2:13][CH:12]=[C:11]([CH3:34])[CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[C:22]([O:23][CH3:24])[C:21]([CH3:25])=[C:20]2[C:16]=1[C:17](=[O:26])[O:18][CH2:19]2

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 72563675HCID 72563675, compound

Product 1

HCID 67011361HCID 67011361, compoundYield 50.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of {5-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-3-methyl-pent-3-enyl}-phosphonic acid diethyl ester (20 mg, 0.039 mmol) in DMF (0.5 mL) and DCM (0.5 mL) was added TMSBr (50.5 μL, 0.39 mmol) followed by 2,6-lutidine (45.3 μL, 0.39 mmol). The reaction was allowed to proceed for one hour when it was complete, as judged by LCMS. The reaction mixture was quenched with MeOH and concentrated to dryness. The residue was purified by preparative reverse-phase HPLC. The fraction containing the desired product was concentrated and treated with 10% TFA/DCM for 5 minutes. After concentration, the residue was purified by preparative reverse-phase HPLC to provide 7 mg (50%) of [5-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-pent-3-enyl]-phosphonic acid as a solid. 1H NMR (300 MHz, CD3OD) δ 1.66-1.78 (m, 5H), 2.10 (s, 3H), 2.16-2.22 (m, 2H), 3.34 (d, J=7.2 Hz, 2H), 3.72 (s, 3H), 5.16 (s, 2H), 5.20 (t, J=7.2 Hz, 1H) ppm; 31P (121.4 MHz, CD3OD) δ 31.57 ppm; MS (m/z) 355 [M−H]−, 357 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with MeOH
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by preparative reverse-phase HPLC
  4. additionThe fraction containing the desired product
  5. concentrationwas concentrated
  6. additiontreated with 10% TFA/DCM for 5 minutes
  7. concentrationAfter concentration
  8. customthe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-a73238515cb04e68a9983aae3617243b
Source dataset
uspto-grants-2015_09
Patent number
US09139604B2

Reaction notes

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