Water → HCID 78322380, compound

HRID 332895Notes

Reaction equation

HRID 332895 reaction equation
OC1C=CC(C2SC3C=C(OC)C=CC=3C=2OC2C=CC(/C=C/C(OC)=O)=CC=2)=CC=1.[OH:32][C:33]1[CH:34]=[CH:35][C:36]2[C:40]([O:41][C:42]3[CH:47]=[CH:46][C:45](/[CH:48]=[CH:49]/[C:50]([O:52]C)=[O:51])=[CH:44][CH:43]=3)=[C:39]([C:54]3[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][CH:55]=3)[S:38][C:37]=2[CH:62]=1.O.[Li+].[OH-]>C1COCC1.CO.C(Cl)Cl>[OH:32][C:33]1[CH:34]=[CH:35][C:36]2[C:40]([O:41][C:42]3[CH:43]=[CH:44][C:45](/[CH:48]=[CH:49]/[C:50]([OH:52])=[O:51])=[CH:46][CH:47]=3)=[C:39]([C:54]3[CH:55]=[CH:56][C:57]([O:60][CH3:61])=[CH:58][CH:59]=3)[S:38][C:37]=2[CH:62]=1

Participants

8

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 86730678HCID 86730678, compoundHCID 86730679HCID 86730679, compound

Product 1

HCID 78322380HCID 78322380, compoundYield 57.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 30 mL vial containing a mixture of (E)-methyl 3-(4-((2-(4-hydroxyphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate and (E)-methyl 3-(4-((6-hydroxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (32 mg, 0.07 mmol) in THF (3 mL), MeOH (1 mL), and H2O (2 mL) was added LiOH (9.14 mg, 0.38 mmol). The reaction mixture was stirred for 60 min at room temperature and then concentrated in vacuo, diluted with water, and acidified to pH 2 with 6 M HCl causing a precipitate to form. The mixture was diluted with 20 mL DCM and 2 mL MeOH. The organic layer was collected (phase separator) and concentrated in vacuo to afford the crude product. The sample was purified by supercritical fluid chromatography (CHIRALCEL® OJ-H column, 45% MeOH in CO2) to afford (E)-3-(4-((6-hydroxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (17 mg, 0.04 mmol, 53% yield) as a white solid. 1H NMR (400 MHz, (CD3)2SO) δ ppm=7.64 (d, J=8.59 Hz, 2H), 7.55-7.62 (m, 2H), 7.51 (d, J=16.17 Hz, 1H), 7.30 (d, J=2.02 Hz, 1H), 7.13 (d, J=8.59 Hz, 1H), 6.90-7.04 (m, 4H), 6.83 (dd, J=2.02, 8.59 Hz, 1H), 6.38 (d, J=16.17 Hz, 1H), 3.75 (s, 3H). LC/MS (m/z, M-H): 417.5.

Workup

  1. additionTo a 30 mL vial containing
  2. concentrationconcentrated in vacuo
  3. additiondiluted with water
  4. customto form
  5. customThe organic layer was collected (phase separator)
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product
  8. customThe sample was purified by supercritical fluid chromatography (CHIRALCEL® OJ-H column, 45% MeOH in CO2)

Sources & evidence

ORD record
ord-356c8047c3184fe6b5a02b70f24eafa3
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

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