Hydrochloric Acid → di-tert-butyl (2S,2'S)-2,2'-{[(1S,4S)-1,4-dihydroxybutane-1,4-diyl]bis (6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate

HRID 1411435

Reaktionsgleichung

Reaktionsgleichung von HRID 1411435
C1(C(C2C=CC=CC=2)([C@H]2CCCN2)O)C=CC=CC=1.COB(OC)OC.B.C(N(CC)C1C=CC=CC=1)C.[O:39]=[C:40]([C:75]1[C:103]([F:104])=[CH:102][C:78]2[N:79]([CH2:94][O:95][CH2:96][CH2:97][Si:98]([CH3:101])([CH3:100])[CH3:99])[C:80]([C@@H:82]3[CH2:86][CH2:85][CH2:84][N:83]3[C:87]([O:89][C:90]([CH3:93])([CH3:92])[CH3:91])=[O:88])=[N:81][C:77]=2[CH:76]=1)[CH2:41][CH2:42][C:43]([C:45]1[C:73]([F:74])=[CH:72][C:48]2[N:49]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:50]([C@@H:52]3[CH2:56][CH2:55][CH2:54][N:53]3[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[N:51][C:47]=2[CH:46]=1)=[O:44].CO.Cl>C1COCC1>[OH:44][C@H:43]([C:45]1[C:73]([F:74])=[CH:72][C:48]2[N:49]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:50]([C@@H:52]3[CH2:56][CH2:55][CH2:54][N:53]3[C:57]([O:59][C:60]([CH3:61])([CH3:62])[CH3:63])=[O:58])=[N:51][C:47]=2[CH:46]=1)[CH2:42][CH2:41][C@@H:40]([C:75]1[C:103]([F:104])=[CH:102][C:78]2[N:79]([CH2:94][O:95][CH2:96][CH2:97][Si:98]([CH3:99])([CH3:100])[CH3:101])[C:80]([C@@H:82]3[CH2:86][CH2:85][CH2:84][N:83]3[C:87]([O:89][C:90]([CH3:91])([CH3:92])[CH3:93])=[O:88])=[N:81][C:77]=2[CH:76]=1)[OH:39]

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 8470Trimethyl borateHCID 83312Diethylaniline-boraneHCID 70453712-Pyrrolidinemethanol, alpha,alpha-diphenyl-, (R)-HCID 58403875di-tert-butyl (2S,2'S)-2,2'-[(1,4-dioxobutane-1,4-diyl)bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)]dipyrrolidine-1-carboxylate

Produkt 1

HCID 58403917di-tert-butyl (2S,2'S)-2,2'-{[(1S,4S)-1,4-dihydroxybutane-1,4-diyl]bis (6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylateAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (R)-(+)-α,α-diphenyl-2-pyrrolidinemethanol (59.9 mg, 0.24 mmol) in THF (2.8 mL) was added trimethylborate (0.034 mL, 0.31 mmol), and the resultant solution was stirred for 90 minutes. The solution was cooled to 0° C. and N,N-diethylaniline borane (0.4 mL, 2.2 mmol) was added in portions over 30 minutes with stirring continued at 0° C. This solution was added via cannula to a 0° C. solution of di-tert-butyl (2S,2′S)-2,2′-[(1,4-dioxobutane-1,4-diyl)bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)]dipyrrolidine-1-carboxylate (265 mg, 0.28 mmol) in THF (2.8 mL) and then warmed to room temperature and stirred for 16 hours. The solution was cooled to 0° C. and CH3OH (0.09 mL, 2.2 mmol) was added, and the solution was warmed to room temperature and stirred for 2 hours. 1N HCl was added, and the aqueous solution was extracted with EtOAc. The combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification was run by flash chromatography (0-3% CH3OH/CH2Cl2) to give the title compound (248 mg, 0.26 mmol, 93%).

Aufarbeitung

  1. customcontinued at 0° C
  2. temperaturewarmed to room temperature
  3. stirringstirred for 16 hours
  4. temperatureThe solution was cooled to 0° C.
  5. temperaturethe solution was warmed to room temperature
  6. stirringstirred for 2 hours
  7. extractionthe aqueous solution was extracted with EtOAc
  8. washThe combined extracts were washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification

Quellen und Nachweise

ORD-Eintrag
ord-b6872ea99d394f858c66c33f93ce2083
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921514B2

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