Hydrochloric Acid → (Z)-2-Methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic Acid

HRID 902455Notes

Reaction equation

C[O:2][C:3](=[O:32])/[C:4](/[O:30][CH3:31])=[CH:5]/[C:6]1[C:11]2[S:12][CH:13]=[CH:14][C:10]=2[C:9]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:8][CH:7]=1.[OH-].[K+].Cl>CO.O>[CH3:31][O:30]/[C:4](=[CH:5]\[C:6]1[C:11]2[S:12][CH:13]=[CH:14][C:10]=2[C:9]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:8][CH:7]=1)/[C:3]([OH:32])=[O:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 45.81 g of (Z)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-acrylic acid methyl ester (100.9 mmol) in 920 ml of methanol, a solution of 40.15 g of potassium hydroxide (615.3 mmol) in 92 ml of water was added within 5 minutes. The white suspension was stirred for 90 min at 100° C. The formed yellowish reaction solution was cooled to 60° C., 54 ml of conc. hydrochloric acid were added dropwise within 5 min (pH 3-4) and the resulting thick suspension was cooled to 0° C. The solid was filtered off and washed with 1000 ml water in four portions. The filter cake was suspended in 920 ml of ethanol at 80° C. for 1 h and after at 0° C. for 2 h. The white crystals were filtered off, washed with 300 ml of cold (−15° C.) ethanol in two portions and dried to constant weight (20° C./5 mbar/16 h) to afford 41.66 g (95%) of the title compound with a purity of >99.9% according to HPLC (method described in Example 10). m.p.: 189-190° C. MS: 434.2 (M−H)−. 1H-NMR (CDCl3): 2.41 (s, 3H); 3.11 (t, J=6.6, 2H); 3.79 (s, 3H); 4.47 (t, J=6.8, 2H); 6.88 (d, J=8.8, 1H); 7.30-7.40 (m, 2H); 7.40-7.47 (m, 3H); 7.49 (d, J=5.6, 1H); 8.00-8.10 (m, 2H); 8.12 (d, J=8.4, 1H); COOH very br.

Workup

temperatureThe formed yellowish reaction solution was cooled to 60° C.
temperaturethe resulting thick suspension was cooled to 0° C
filtrationThe solid was filtered off
washwashed with 1000 ml water in four portions
waitThe filter cake was suspended in 920 ml of ethanol at 80° C. for 1 h
waitafter at 0° C. for 2 h
filtrationThe white crystals were filtered off
washwashed with 300 ml of cold (−15° C.) ethanol in two portions
customdried to constant weight (20° C./5 mbar/16 h)

Sources & evidence

ORD record: ord-1d439d218211495b85814d49df286c13
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07365207B2

Reaction notes

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