Tetrahydrofuran → ethyl rel-(1R,2S)-4-[1-(5-chloropyrimidin-2-yl)ethenyl]-2-methylcyclohexanecarboxylate

HRID 1482897Notes

Reaction equation

HRID 1482897 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[N:6][C:7]([C:10]([CH:12]2[CH2:17][CH2:16][C@@H:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([CH3:23])[CH2:13]2)=O)=[N:8][CH:9]=1.[Cl-].[NH4+].[CH2:26]1COCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:3][C:4]1[CH:5]=[N:6][C:7]([C:10]([CH:12]2[CH2:17][CH2:16][C@@H:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([CH3:23])[CH2:13]2)=[CH2:26])=[N:8][CH:9]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 118126863ethyl rel-(1R,2S)-4-[(5-chloropyrimidin-2-yl)carbonyl]-2-methylcyclohexanecarboxylate

Product 1

HCID 118126819ethyl rel-(1R,2S)-4-[1-(5-chloropyrimidin-2-yl)ethenyl]-2-methylcyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 74505Methyltriphenyliphosphonium bromideCatalyst

Conditions

Temperature
25 °C

Procedure

To a solution of methyltriphenylphosphonium bromide (2.22 g, 6.20 mmol) in THF (22 mL) was added sodium hydride (0.24 g, 6.2 mmol, 10 wt %) at 0° C. After being stirred at 25° C. for 3 hours, ethyl rel-(1R,2S)-4-[(5-chloropyrimidin-2-yl)carbonyl]-2-methylcyclohexanecarboxylate (0.62 g, 2 mmol) was added in one portion at 0° C. The reaction mixture was stirred at 20° C. for 6 hours and then saturated aqueous ammonium chloride was added. The reaction mixture was extracted with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (ethyl acetate/petroleum ether) to give ethyl rel-(1R,2S)-4-[1-(5-chloropyrimidin-2-yl)ethenyl]-2-methylcyclohexanecarboxylate. MS ESI calc'd for C16H22ClN2O2[M+H]+ 309. found 309. 1H NMR: (400 MHz, CD3OD) δ 8.80-8.74 (m, 2H), 6.45-6.40 (m, 1H), 5.55-5.49 (m, 1H), 4.19-4.12 (m, 2H), 2.72-2.47 (m, 2H), 1.87-1.74 (m, 3H), 1.73-1.58 (m, 2H), 1.31-1.25 (m, 4H), 1.22-1.18 (m, 1H), 1.04-1.00 (m, 3H).

Workup

  1. stirringThe reaction mixture was stirred at 20° C. for 6 hours
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by prep-TLC (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-f447ef7ecf2948a38cc69411f5f147c1
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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