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

HRID 2190006Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2190006
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([O:33]C(=O)C5C=CC([N+]([O-])=O)=CC=5)[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1.O[Li].O>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([OH:33])[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1

Komponenten

4

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 68762968HCID 68762968, Verbindung

Produkt 1

HCID 68759438tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylateAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21881883Oxolane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of tert-butyl 5-chloro-1-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.020 g, 0.032 mmol) in THF:H2O (2:1, 0.3 mL) was cooled to about 0° C. and treated with LiOH—H2O (0.0027 g, 0.065 mmol). The reaction was stirred at about 0° C. for about 5 minutes, followed by about room temperature for 1.5 hours. The reaction was concentrated and diluted with saturated NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. Crude residue was purified by preparative HPLC to yield tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.005 g, 36%). LCMS (APCI+) m/z 471, 473 [M+H]+; Rt=4.11 min.

Aufarbeitung

  1. waitfollowed by about room temperature for 1.5 hours
  2. concentrationThe reaction was concentrated
  3. additiondiluted with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrude residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-58ab98c0a0fe4e8da405a010665f595b
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08324221B2

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