Diisopropylethylamine → 3-{4-[3-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propyl]-2,6-dimethyl-phenyl}-propionic acid

HRID 1013445Notes

Reaction equation

HRID 1013445 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:24])[CH:9]=[CH:10][C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[C:13]([CH3:23])[CH:12]=2)=[C:5]2[CH2:25][CH2:26][C:27]([CH3:30])([CH3:29])[CH2:28][C:4]=12)[CH3:2].CCN(C(C)C)C(C)C>C(O)C.[Pd]>[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:24])[CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[C:13]([CH3:23])[CH:12]=2)=[C:5]2[CH2:25][CH2:26][C:27]([CH3:29])([CH3:30])[CH2:28][C:4]=12)[CH3:2]

Participants

5

Reactant 2

HCID 81531DiisopropylethylamineHCID 673169693-{4-[3-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propenyl]-2,6-dimethyl-phenyl}-propionic acid

Product 1

HCID 161128733-{4-[3-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propyl]-2,6-dimethyl-phenyl}-propionic acidYield 74.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of 3-{4-[3-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propenyl]-2,6-dimethyl-phenyl}-propionic acid (610 mg, 1.44 mmol) and DIPEA (204 mg, 1.58 mmol) in ethanol (30 mL) is added Pd/C (300 mg, 10% Pd, moistened with 50% water). The slurry is stirred at rt for 18 h under 1 atm H2. The mixture is filtered and the filtrate is evaporated. The crude product is purified by prep. HPLC (Grom-Sil 120 ODS-4-HE, 30×75 mm, 10 μm, acetonitrile/water (0.5% HCOOH), 20% to 95% acetonitrile) to give 3-{4-[3-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propyl]-2,6-dimethyl-phenyl}-propionic acid (460 mg) as a colourless lyophilisate; LC-MS: tR=1.15 min; [M+1]=427.40; 1H NMR (CDCl3): δ 6.91 (s, 2H), 3.10-2.90 (m, 8H), 2.73 (q, J=7.6 Hz, 2H), 2.53-2.46 (m, 2H), 2.32 (s, 6H), 2.30 (s, 2H), 1.54 (t, J=7.0 Hz, 2H), 1.28 (t, J=7.6 Hz, 3H), 0.97 (s, 6H).

Workup

  1. filtrationThe mixture is filtered
  2. customthe filtrate is evaporated
  3. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-7a35fb1cd0be4dd7b7e45d7f461bda02
Source dataset
uspto-grants-2011_07
Patent number
US07981924B2

Reaction notes

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