Isopropanol → (E)-isopropyl 3-(4-((6-((tert-butyldimethylsilyl)oxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

HRID 632675Notes

Reaction equation

HRID 632675 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27])=[CH:20][CH:19]=3)=[C:15]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:37])[CH3:36])[S:14][C:13]=2[CH:38]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:39][CH:40](O)[CH3:41].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C)C1C=CN=CC=1.CCOC(C)=O.CCCCCCC>[Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:16]([O:17][C:18]3[CH:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]([O:28][CH:40]([CH3:41])[CH3:39])=[O:27])=[CH:20][CH:19]=3)=[C:15]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:36])[CH3:37])[S:14][C:13]=2[CH:38]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 3776IsopropanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131735440(E)-3-(4-((6-((tert-butyldimethylsilyl)oxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

Product 1

HCID 131735441(E)-isopropyl 3-(4-((6-((tert-butyldimethylsilyl)oxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylateYield 55%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a solution of (E)-3-(4-((6-((tert-butyldimethylsilyl)oxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (59.6 mg, 0.109 mmol) in DCM (2.5 mL) was added i-PrOH (0.034 mL, 0.438 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (84 mg, 0.438 mmol) and 4-dimethylaminopyridine (8.02 mg, 0.066 mmol). The resulting mixture was stirred at room temperature for 75 min after which time the reaction was quenched by addition of water and diluted with DCM. The phases were separated and the aqueous layer was further extracted with DCM (3×). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography (SiO2, 0-30% EtOAc/Heptane) to (E)-isopropyl 3-(4-((6-((tert-butyldimethylsilyl)oxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (35 mg, 0.060 mmol, 55% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.49 (d, J=16.0 Hz, 1H), 7.32-7.17 (m, 7H), 7.10-7.03 (m, 1H), 6.79 (d, J=8.8 Hz, 3H), 6.18 (d, J=16.1 Hz, 1H), 5.05 (p, J=6.2 Hz, 1H), 3.18 (p, J=6.8 Hz, 1H), 1.23 (d, J=6.4 Hz, 6H), 1.11 (d, J=6.8 Hz, 6H), 0.95 (s, 9H), 0.18 (s, 6H).

Workup

  1. customwas quenched by addition of water
  2. additiondiluted with DCM
  3. customThe phases were separated
  4. extractionthe aqueous layer was further extracted with DCM (3×)
  5. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bae2ced172b34e209425d2be1200491a
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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