Tetrahydrofuran → tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 529065Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 529065
C([O:4][CH:5]1[C:9]2[N:10]=[CH:11][N:12]=[C:13]([N:14]3[C:34]4[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=4)[C:16]4([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[CH2:15]3)[C:8]=2[C@H:7]([CH3:36])[CH2:6]1)(=O)C.C1COCC1.O[Li].O>O>[Cl:35][C:31]1[CH:30]=[C:29]2[C:16]3([CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]3)[CH2:15][N:14]([C:13]3[C:8]4[C@H:7]([CH3:36])[CH2:6][CH:5]([OH:4])[C:9]=4[N:10]=[CH:11][N:12]=3)[C:34]2=[CH:33][CH:32]=1

Komponenten

5

Edukt 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 69810145HCID 69810145, Verbindung

Produkt 1

HCID 69809362tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylateAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 1-((5R)-7-acetoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylate (0.170 g, 0.331 mmol) in 2:1 THF:H2O (1.8 mL) was cooled to about 0° C. LiOH—H2O (0.034 g, 0.83 mmol) was added and the reaction was stirred at about room temperature for 4 hours. The reaction was quenched by the addition of 1N HCl to pH 6. The aqueous phase was extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by column chromatography (30-70% EtOAc/Hexane) to yield tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.065 g, 42%). LCMS (APCI+) m/z 471, 473 [M+H]+; Rt=3.82 min.

Aufarbeitung

  1. customThe reaction was quenched by the addition of 1N HCl to pH 6
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washThe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by column chromatography (30-70% EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-e51f08ec6ae44c09a9cb5bd74b677d1b
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346805B2

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