Hydrochloric Acid → HCID 66747853, compound

HRID 2402170Notes

Reaction equation

HRID 2402170 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:5][C:6]1[C:10]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:9]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[S:8][C:7]=1[C:25]([O:27]CC)=[O:26].C1COCC1.[OH-].[Na+].Cl>CCOC(C)=O.O.C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[Cl:33])[CH2:5][C:6]1[C:10]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[C:9]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[S:8][C:7]=1[C:25]([OH:27])=[O:26]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66747336HCID 66747336, compound

Product 1

HCID 66747853HCID 66747853, compoundYield 78%

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of ethyl 3-(3,4-dichlorobenzyl)-5-(morpholin-4-yl)-4-(phenylethynyl)thiophene-2-carboxylate (0.041 g, 0.082 mmol in THF (2.00 mL, 24.6 mmol) and methanol (0.37 mL, 9.1 mmol) was added 1.000 M of sodium hydroxide in water (1.684 mL, 1.684 mmol) and the resulting biphasic mixture was stirred at room temp for 2 days. The pH was carefully adjusted to 3.0 via addition of 1N HCl (monitored in real time with a pH meter), and the reaction mixture was transferred to a separatory funnel. The mixture was diluted with EtOAc (40 mL) and water (15 mL), and the layers were separated. The aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were washed with brine, then dried over Na2SO4, filtered, and concentrated. Column chromatography (eluent: 0-5% MeOH:DCM) afforded 3-(3,4-dichlorobenzyl)-5-(morpholin-4-yl)-4-(phenylethynyl)thiophene-2-carboxylic acid (30 mg, 78% yield). LCMS: (FA) ES+ 472, 473, 474; 1H NMR (400 MHz, DMSO) δ 12.92 (s, 1H), 7.55-7.50 (m, 2H), 7.43-7.34 (m, 5H), 7.21 (dd, J=8.3, 2.0 Hz, 1H), 4.39 (s, 2H), 3.81-3.68 (m, 4H), 3.56-3.42 (m, 4H).

Workup

  1. customwas transferred to a separatory funnel
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-11fba835001043f5827408a298d0c3eb
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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