Acetic Anhydride → 2-Acetyl-3-hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enone

HRID 1917475Notes

Reaction equation

HRID 1917475 reaction equation
[OH:1][C:2]1[CH2:7][CH:6]([C:8]2[S:9][CH:10]=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[N:14]=2)[CH2:5][C:4](=[O:21])[CH:3]=1.[C:22](OC(=O)C)(=[O:24])[CH3:23].CCN(CC)CC>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:22]([C:3]1[C:2](=[O:1])[CH2:7][CH:6]([C:8]2[S:9][CH:10]=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[N:14]=2)[CH2:5][C:4]=1[OH:21])(=[O:24])[CH3:23]

Participants

6

Reactant 3

HCID 7918Acetic Anhydride2×HCID 8471TriethylamineHCID 579991803-Hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enone

Product 1

HCID 579990932-Acetyl-3-hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enoneYield 31%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a 200 mL recovery flask was added 3-hydroxy-5-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)cyclohex-2-enone (30F, 4.9 g, 16.3 mmol, 1.0 eq.), CH2Cl2 (100 mL), acetic anhydride (2.15 g, 21.1 mmol, 1.3 eq.), Et3N (6.8 mL, 48.8 mmol, 3.0 eq.), and DMAP (catalytic). The reaction mixture was stirred overnight at room temperature whereupon LC/MS showed two signals corresponding to M+H=344. Additional acetic anhydride (0.5 mL, 5.3 mmol, 0.32 eq.) was added and the reaction mixture was heated for 6 h at 40° C. LC/MS analysis showed the reaction to be complete whereupon the mixture was concentrated to a solid and purified via flash chromatography (70% CH2Cl2/Hex to 100% CH2Cl2) to yield a dark orange solid 30G (1.72 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.52-2.57 (m, 3H) 2.83 (m, 2H) 3.09 (m, 2H) 3.78 (s, 3H) 4.68 (m, 1H) 6.74 (d, J=8.34 Hz, 1H) 7.32 (d, J=7.33 Hz, 1H) 7.41-7.47 (m, 1H) 7.51 (d, J=5.31 Hz, 1H) 7.76 (t, J=7.96 Hz, 1H). ESI-MS: m/z 344.3 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated for 6 h at 40° C
  2. customthe reaction
  3. concentrationwas concentrated to a solid
  4. custompurified via flash chromatography (70% CH2Cl2/Hex to 100% CH2Cl2)

Sources & evidence

ORD record
ord-03934a8409eb446582a85d2fa5659524
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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