Hydrochloric Acid → (2-{[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyl]-methanesulfonyl-amino}-ethyl)-phosphonic Acid

HRID 2114218Notes

Reaction equation

HRID 2114218 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][N:11]([S:37]([CH3:40])(=[O:39])=[O:38])[CH2:12][C:13]([CH3:36])=[CH:14][CH2:15][C:16]1[C:17]([O:29]CC[Si](C)(C)C)=[C:18]2[C:22](=[C:23]([CH3:27])[C:24]=1[O:25][CH3:26])[CH2:21][O:20][C:19]2=[O:28])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C.Cl>C(#N)C.CCOC(C)=O>[OH:29][C:17]1[C:16]([CH2:15][CH:14]=[C:13]([CH3:36])[CH2:12][N:11]([S:37]([CH3:40])(=[O:38])=[O:39])[CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[C:24]([O:25][CH3:26])[C:23]([CH3:27])=[C:22]2[C:18]=1[C:19](=[O:28])[O:20][CH2:21]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 76541030[2-(Methanesulfonyl-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enyl}-amino)-ethyl]-phosphonic Acid Diethyl Ester

Product 1

HCID 67011096(2-{[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enyl]-methanesulfonyl-amino}-ethyl)-phosphonic AcidYield 73.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of [2-(methanesulfonyl-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enyl}-amino)-ethyl]-phosphonic acid diethyl ester (18 mg, 0.029 mmol) in acetonitrile (0.5 mL) was stirred with TMSBr (38 μL, 0.29 mmol) and 2,6-lutidine (34 μL, 0.29 mmol) for 2 hours at room temperature. The reaction was worked up by addition of EtOAc and aqueous 1N HCl. The organic layer was washed with brine and the solvent was removed in vacuo. The residue was suspended in a solution of 10% TFA-CH2Cl2 for 10 minutes before it was dried to provide 9.9 mg of the desired product (73%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.76 (s, 3H), 1.76-1.88 (m, 2H), 2.10 (s, 3H), 2.87 (s, 3H), 3.24-3.35 (m, 2H), 3.39 (d, 2H, J=7 Hz), 3.65 (s, 2H), 3.75 (s, 3H), 5.22 (s, 2H), 5.41-5.48 (m, 1H) ppm; 31P (121.4 MHz, DMSO-d6) δ 21.4 ppm; MS (m/z) 464.1 [M+H]+.

Workup

  1. washThe organic layer was washed with brine
  2. customthe solvent was removed in vacuo
  3. customwas dried

Sources & evidence

ORD record
ord-f0370682e8614f7aba6f3a7cd838ebcd
Source dataset
uspto-grants-2008_10
Patent number
US07432261B2

Reaction notes

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