Potassium Carbonate → 3-[(5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(s)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid

HRID 548773Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][C@@H:12]([CH3:16])[CH2:13][O:14][CH3:15])[CH:10]=1)[C:5]([OH:7])=[O:6].F[C:18]1[CH:30]=[CH:29][C:21]2[S:22](=[O:28])(=[O:27])[CH2:23][CH2:24][CH2:25][O:26][C:20]=2[CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:28]=[S:22]1(=[O:27])[C:21]2[CH:29]=[CH:30][C:18]([O:1][C:2]3[CH:3]=[C:4]([CH:8]=[C:9]([O:11][C@@H:12]([CH3:16])[CH2:13][O:14][CH3:15])[CH:10]=3)[C:5]([OH:7])=[O:6])=[CH:19][C:20]=2[O:26][CH2:25][CH2:24][CH2:23]1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 3-hydroxy-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}benzoic acid (0.245 g, 1.08 mmol), 8-fluoro-3,4-dihydro-2H-1,5-benzoxathiepine 5,5-dioxide (235 mg, 1.08 mmol) and potassium carbonate (299 mg, 2.17 mmol) in acetonitrile (7.8 mL) was heated in a microwave reactor at 160° C. for 5 hours. The mixture was reduced in vacuo and the residue purified by preparative HPLC (on a C18 reversed phase using 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA) as eluant) to give the desired compound as a beige solid (222 mg). 1H NMR δ (d6-DMSO): 1.22 (d, 3H), 2.22-2.24 (m, 2H), 3.17 (s, 3H), 3.43-3.58 (m, 4H), 4.03-4.16 (m, 1H), 4.16-4.25 (m, 2H), 4.63-4.73 (m, 1H), 6.80-6.85 (m, 1H) 6.90-7.01 (m, 2H), 7.15 (s, 1H), 7.35 (s, 1H), 7.83 (d, 1H); m/z 421 (M−H)−

Workup

customthe residue purified by preparative HPLC (on a C18 reversed phase

Sources & evidence

ORD record: ord-cf32fa98b93a480ba36b5a3836d80a2c
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943607B2

Reaction notes

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