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Sodium cyanoborohydride → methyl (7S)-7-[(1-{2-[(tert-butoxycarbonyl)(methyl)amino]ethyl}pyrrolidin-2-yl)methoxy]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 1669451
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1669451
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:33]([O:35][CH3:36])=[O:34])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][C@@H:16]([O:26][CH2:27][CH:28]2[CH2:32][CH2:31][CH2:30][NH:29]2)[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:37][N:38]([CH2:46][CH:47]=O)[C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].[BH3-]C#N.[Na+]>CO.C1COCC1.CC(O)=O>[C:41]([O:40][C:39]([N:38]([CH3:37])[CH2:46][CH2:47][N:29]1[CH2:30][CH2:31][CH2:32][CH:28]1[CH2:27][O:26][C@H:16]1[CH2:15][N:14]2[C:13]3[CH:12]=[C:11]([C:33]([O:35][CH3:36])=[O:34])[CH:10]=[CH:9][C:8]=3[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[C:21]2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17]1)=[O:45])([CH3:44])([CH3:43])[CH3:42]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 5003444Sodium cyanoborohydride2×HCID 10725881tert-butyl N-methyl-N-(2-oxoethyl)carbamate2×HCID 67345272methyl (7S)-14-cyclohexyl-7-(pyrrolidin-2-ylmethoxy)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Produkt 1

HCID 67344077methyl (7S)-7-[(1-{2-[(tert-butoxycarbonyl)(methyl)amino]ethyl}pyrrolidin-2-yl)methoxy]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution (0.02 M) of methyl (7S)-14-cyclohexyl-7-(pyrrolidin-2-ylmethoxy)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate in MeOH/THF (2/1), AcOH (cat.) was added followed by tert-butyl methyl(2-oxoethyl)carbamate (2 eq, prepared as described in Tetrahedron 2002, 58, 1719-1737). The reaction was stirred at RT for 30 min at which point NaCNBH3 (2 eq) was added and the mixture was stirred at 40° C. for 1 h. Additional tert-butyl methyl(2-oxoethyl)carbamate (1 eq) and NaCNBH3 (5 eq) were added and the reaction was stirred for further 30 min at 40° C. The reaction was quenched by adding sat. aq. NaHCO3. The aqueous phase was extracted with EtOAc and the combined organics washed with brine before being dried (Na2SO4), filtered and concentrated in vacuo. The product was used in the subsequent step without further purification. (ES+) m/z 646 (M+H)+

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction was stirred for further 30 min at 40° C
  3. customThe reaction was quenched
  4. additionby adding sat. aq. NaHCO3
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organics washed with brine
  7. dry with materialbefore being dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe product was used in the subsequent step without further purification

Quellen und Nachweise

ORD-Eintrag
ord-02155ec66ca24895b80eacf1fe381c50
Quelldatensatz
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07989438B2

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