Thiophenol → (E)-3-(4-((6-hydroxy-2-(2-(methoxymethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

HRID 632704Notes

Reaction equation

HRID 632704 reaction equation
C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH2:29][O:30][CH3:31])[S:8][C:7]=2[CH:32]=1.C1(S)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O.CCOC(C)=O>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH2:29][O:30][CH3:31])[S:8][C:7]=2[CH:32]=1

Participants

6

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 118574955(E)-3-(4-((6-methoxy-2-(2-(methoxymethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

Product 1

HCID 118574963(E)-3-(4-((6-hydroxy-2-(2-(methoxymethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acidYield 6.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of (E)-3-(4-((6-methoxy-2-(2-(methoxymethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (45.9 mg, 0.103 mmol) in N-methyl-2-pyrrolidone (1.0 mL) was added thiophenol (0.016 mL, 0.154 mmol) and K2CO3 (14.21 mg, 0.103 mmol). The resulting mixture was subjected to microwave irradiation at 200° C. for 90 min after which time the reaction was diluted with EtOAc and filtered. The filtrate was concentrated in vacuo and the crude material was purified by was purified by reverse phase HPLC (basic condition, 0.1% NH4OH in CH3CN/H2O) to afford (E)-3-(4-((6-hydroxy-2-(2-(methoxymethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (3.0 mg, 0.00645 mmol, 6% yield). 1H NMR (400 MHz, CD3OD) δ ppm=7.47 (d, J=7.7 Hz, 1H), 7.40-7.31 (m, 4H), 7.31-7.21 (m, 4H), 6.86 (dd, J=8.7, 2.1 Hz, 1H), 6.79 (d, J=8.4 Hz, 2H), 6.35 (d, J=15.9 Hz, 1H), 4.53 (s, 2H), 3.29 (s, 3H). HRMS (m/z. M+H2O): 450.1355.

Workup

  1. customirradiation at 200° C. for 90 min after which time the reaction
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe crude material was purified
  5. customby was purified by reverse phase HPLC (basic condition, 0.1% NH4OH in CH3CN/H2O)

Sources & evidence

ORD record
ord-5a6072ac75c94101a592a8d0b5bbaa80
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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