HCID 118574928, compound → LSZ-102

HRID 632712Notes

Reaction equation

HRID 632712 reaction equation
[F:1][C:2]([C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[C:12]1[S:16][C:15]2[CH:17]=[C:18]([OH:21])[CH:19]=[CH:20][C:14]=2[C:13]=1[O:22][C:23]1[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[C:31]([O:33]C)=[O:32])=[CH:25][CH:24]=1)([F:4])[CH3:3]>C1COCC1.O>[F:1][C:2]([C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[C:12]1[S:16][C:15]2[CH:17]=[C:18]([OH:21])[CH:19]=[CH:20][C:14]=2[C:13]=1[O:22][C:23]1[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[C:31]([OH:33])=[O:32])=[CH:25][CH:24]=1)([F:4])[CH3:3]

Participants

4

Reactant 1

HCID 118574928HCID 118574928, compound

Product 1

HCID 118574930LSZ-102Yield 69.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (E)-methyl 3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (1.4 g, 2.89) in THF (5 mL) and water (3 mL) was added 56% LiOH monohydrate (371 mg, 8.67 mmol). The resulting mixture was stirred at room temperature for 18 h after which time the reaction was concentrated in vacuo to remove THF and the resulting solution was diluted with water and acidified by addition of HCl (1N aq.), causing a precipitate to crash out. The resulting precipitate was filtered to give (E)-3-(4-((2-(2-(1,1-difluoroethyl)-4-fluorophenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid as a white solid which was not purified further (980 mg, 2.021 mmol, 69.9% yield). 1H NMR (400 MHz, CD3OD) δ ppm=1.80 (t, J=18.44 Hz, 3 H), 6.23 (d, J=16.17 Hz, 1 H), 6.71-6.81 (m, 3 H), 7.03 (td, J=8.21, 2.78 Hz, 1 H), 7.08-7.14 (m, 2 H), 7.22-7.32 (m, 2 H), 7.37 (d, J=8.59 Hz, 2 H), 7.47 (d, J=16.17 Hz, 1 H), LC/MS (m/z, M−H): 468.9.

Workup

  1. concentrationwas concentrated in vacuo
  2. customto remove THF
  3. additionthe resulting solution was diluted with water
  4. additionacidified by addition of HCl (1N aq.)
  5. filtrationThe resulting precipitate was filtered

Sources & evidence

ORD record
ord-fd3733441b6a4cb68e2967dff1d3557c
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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