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 540690Notes

Reaction equation

HRID 540690 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-7d7c388f7a7443d7b45fadb0e5e72ed6
Source dataset
uspto-grants-2014_10
Patent number
US08871785B2

Reaction notes

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