Sodium hydride → Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate

HRID 928124Notes

Reaction equation

HRID 928124 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]1[S:13][C:14]([Br:17])=[CH:15][N:16]=1)(=O)OCC)C.O=[C:19]1[CH2:24][CH2:23][CH:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]1>C1COCC1.[Cl-].[NH4+]>[Br:17][C:14]1[S:13][C:12]([CH:11]=[C:19]2[CH2:24][CH2:23][CH:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]2)=[N:16][CH:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 86720195Diethyl[(5-bromo-1,3-thiazol-2-yl)methyl]phosphonate

Product 1

HCID 86720196Ethyl 4-[(5-bromo-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride (60% in mineral oil, 122 mg, 3.06 mmol) in THF (10 mL) was cooled to 0° C., and diethyl[(5-bromo-1,3-thiazol-2-yl)methyl]phosphonate (769 mg, 2.448 mmol) in THF (2 mL) was added dropwise and subsequently stirred at 0° C. for 30 minutes. Ethyl 4-oxocyclohexanecarboxylate (417 mg, 2.448 mmol) in THF (2 mL) was then added, and allowed to warm to room temperature over 2 h. Then, the reaction was diluted with saturated ammonium chloride and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-10% ethyl acetate in hexanes) to afford ethyl 4-[(5-bromo-1,3-thiazol-2-yl)methylidene]cyclohexanecarboxylate as a yellow oil. MS ESI calc'd. for C13H17BrNO2S [M+H]+ 330, 332. found 330, 332. 1H NMR (600 MHz, CDCl3) δ 7.62 (s, 1H), 6.34 (s, 1H), 4.14 (q, J=7.1 Hz, 2H), 3.41-3.33 (m, 1H), 2.60-2.52 (m, 1H), 2.47-2.40 (m, 1H), 2.31-2.19 (m, 2H), 2.12-2.02 (m, 2H), 1.80-1.63 (m, 2H), 1.26 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureto warm to room temperature over 2 h
  2. extractionextracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (0-10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bae7837ed96e4ee7bc8de8b86a485451
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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