Triethyloxonium tetrafluoroborate → [(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243015

Reaktionsgleichung

Reaktionsgleichung von HRID 243015
[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18](=O)[NH2:19])[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:34][C:35]1[CH:36]=[C:37]([NH:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:38](N)=[CH:39][CH:40]=1>C1COCC1>[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([C:18]1[N:42]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=2)[C:37]2[CH:36]=[C:35]([F:34])[CH:40]=[CH:39][C:38]=2[N:19]=1)[CH2:9][O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7216900((S)-2-Benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl esterHCID 681571794-Fluoro-N2-pyridin-2-ylbenzene-1,2-diamine

Produkt 1

HCID 68157510[(R)-2-Benzyloxy-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl esterAusbeute 53,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of ((S)-2-benzyloxy-1-carbamoylethyl)carbamic acid tert-butyl ester (820 mg, 2.8 mmol) in anhydrous THF (10 mL) was added triethyloxonium tetrafluoroborate (550 mg, 2.9 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h. The volatiles were removed in vacuo and the resulting residue redissolved in absolute EtOH (10 mL). To the mixture was added 4-fluoro-N2-pyridin-2-yl-benzene-1,2-diamine (355 mg, 1.7 mmol) and the mixture stirred at 75° C. for 16 h. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic fractions washed with water, dried (MgSO4) and concentrated in vacuo. The resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex) to afford the title compound as a yellow oil (420 mg, 53%). LCMS (Method B): RT 3.95 min [M+H]+ 463.1.

Aufarbeitung

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe resulting residue redissolved in absolute EtOH (10 mL)
  3. stirringthe mixture stirred at 75° C. for 16 h
  4. customThe volatiles were removed in vacuo
  5. customthe resulting residue partitioned between DCM
  6. extractionThe aqueous phase was further extracted with DCM
  7. washthe combined organic fractions washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cHex)

Quellen und Nachweise

ORD-Eintrag
ord-deb2e041a84e4f4eacd05e15f66ce7cf
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

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