Sodium hydride → Ethyl 3-(cyclopropylidenemethyl)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2-carboxylate

HRID 1006273

Reaktionsgleichung

Reaktionsgleichung von HRID 1006273
[H-].[Na+].[Br-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH:11]2[CH2:13][CH2:12]2)C=CC=CC=1.[CH:26]([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]([CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=2)[C:29]=1[C:48]([O:50][CH2:51][CH3:52])=[O:49])=O>O1CCCC1>[C:11]1(=[CH:26][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:46])([F:45])[F:47])[CH:39]=3)[C:29]=2[C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:13][CH2:12]1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 2723931Cyclopropyltriphenylphosphonium bromideHCID 22676825ethyl 3-formyl-1-[3-(trifluoromethyl)benzyl]-1H-indole-2-carboxylate

Produkt 1

HCID 22676741Ethyl 3-(cyclopropylidenemethyl)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (60% dispersion in mineral oil, 128 mg, 3.20 mmol) was suspended in anhydrous tetrahydrofuran (10 mL) and cooled to 0° C. Triphenyl-cyclopropylphosphonium bromide (1.23 g, 3.20 mmol) was added as a solid all at once, and the mixture was allowed to stir at room temperature. Once gas evolution ceased, a tetrahydrofuran solution of ethyl 3-formyl-1-[3-(trifluoromethyl)benzyl]-1H-indole-2-carboxylate (Example 40, 1.0 g, 2.7 mmol) was added, the mixture was stirred for 15 hours, and the resulting mixture was partitioned between water and ethyl acetate. Layers were separated, and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated. The resulting crude oil was purified by flash chromatography on silica gel eluted with 5% ethyl acetate/hexane. The title compound was collected as a bright yellow oil (403 mg, 38%). The product had: 1H NMR (300 MHz, CDCl3) δ 8.04 (d, 1 H), 7.53 (s, 1 H), 7.41-7.38 (m, 2 H), 7.29-7.20 (m, 3 H), 7.15-7.12 (m, 1 H), 7.05 (d, 1 H), 5.72 (s, 2 H), 4.27 (q, 2 H), 1.50-1.45 (m, 2 H), 1.25 (t, 3 H), 0.83-0.76 (m, 2 H); mass spectroscopy gave MH+=400.2 (calc'd exact mass for C23H20F3NO2=399.14).

Aufarbeitung

  1. stirringthe mixture was stirred for 15 hours
  2. customthe resulting mixture was partitioned between water and ethyl acetate
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting crude oil was purified by flash chromatography on silica gel
  8. washeluted with 5% ethyl acetate/hexane
  9. customThe title compound was collected as a bright yellow oil (403 mg, 38%)
  10. custommass spectroscopy gave MH+=400.2 (calc'd exact mass for C23H20F3NO2=399.14)

Quellen und Nachweise

ORD-Eintrag
ord-d8ef65c427d64508a6bf92a2a235b0b8
Quelldatensatz
uspto-grants-2004_09
Patentnummer
US06787651B2

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