Water → 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester

HRID 2078688Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2078688
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](C)(C)[O:18][SiH2]C(C)(C)C)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:26]1[C:27]2[S:40][CH:39]=[CH:38][C:28]=2[N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][OH:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:26]1[C:27]2[S:40][CH:39]=[CH:38][C:28]=2[N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:30]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 131727412Tert-butyl 3-[5-(2-tert-butylsilyloxypropan-2-yl)-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]thieno[3,2-c]pyrazole-1-carboxylate2×

Produkt 1

HCID 576372852-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl esterAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(tert-butyl-dimethyl-silanyloxymethyl)-indole-1-carboxylic acid tert-butyl ester [3.8 g, 6.51 mmol, Intermediate (9)]) in anhydrous tetrahydrofuran (40 mL) is cooled to 0° C. To it is added tetrabutylammonium fluoride (1M in tetrahydrofuran, 10 mL) drop wise. Stirred at 0° C. for 20 minutes then at room temperature for 20 minutes. Water (20 mL) is added and extracted three times with ethyl acetate (30 mL). The combined ethyl acetate phases are washed with brine and dried over sodium sulfate. The residue is chromatographed on 35 g silica gel (10-50% ethyl acetate in heptane) to give 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester [2.63 g, 85%, Intermediate (10)] as white solid; 1H NMR [(CD3)2SO)]: δ 8.05 (2H, m), 7.62 (1H, s), 7.38 (2H, m), 7.02 (1H, s), 5.21 (1H, t), 4.6 (2H, d), 1.64 (9H, s), 1.25 (9H, s); LC/MS: 470 (M+H).

Aufarbeitung

  1. waitat room temperature for 20 minutes
  2. extractionextracted three times with ethyl acetate (30 mL)
  3. washThe combined ethyl acetate phases are washed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe residue is chromatographed on 35 g silica gel (10-50% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-c1fba0f003524a1981d14b1821be8f28
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07928231B2

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