Morpholine → HCID 68525553, compound

HRID 1990104Notes

Reaction equation

HRID 1990104 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([S:20][CH3:21])=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1)=[O:5])[CH3:2].[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([S:20][CH3:21])=[C:9]([C:18]#[N:19])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:13][CH:12]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 19660Carbonate IonHCID 634876Binap, (A+-)-HCID 68524438HCID 68524438, compound

Product 1

HCID 68525553HCID 68525553, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Combine 3-(4-Iodophenyl)-4-cyano-5-methylsulfanyl-thiophene-2-carboxylic acid ethyl ester (50 mg, 0.12 mmol), morpholine (20 μl, 0.23 mmol), Pd2(dba)3 (3.5 mg, 0.006 mmol), cessium carbonate (53 mg, 0.16 mmol) and (+)-BINAP (5.4 mg, 0.009 mmol) in anhydrous toluene (1 ml) and stir at 100° C. for 12 hours. Cool the reaction mixture to room temperature, filtered through celite and washed with ethyl acetate. Evaporate the solvent and purify the residue by column chromatography (silica gel) eluting with ethyl acetate:hexane 1:3 to provide the title compound (22 mg, 49%): 1H NMR (CDCl3, 200 MHz): δ 7.37 (d, 2H, J=8.9); 6.99 (d, 2H, J=8.9); 4.22 (q, 2H, J=7.2); 3.89 (m, 4H); 3.28 (m, 4H); 2.71 (s, 3H); 1.24 (t, 3H, J=7.2).

Workup

  1. filtrationfiltered through celite
  2. washwashed with ethyl acetate
  3. customEvaporate the solvent
  4. custompurify the residue by column chromatography (silica gel)
  5. washeluting with ethyl acetate:hexane 1:3

Sources & evidence

ORD record
ord-d314b1fb951947abbbd2e777075b02d9
Source dataset
uspto-grants-2010_01
Patent number
US07642361B2

Reaction notes

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