Borane;tetrahydrofuran → tert-Butyl (2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 633343Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 633343
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][C@H:9]1[C:15](O)=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].B.C1COCC1>C1COCC1>[F:14][C:11]1([F:13])[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([CH2:15][OH:16])[CH2:10]1

Komponenten

4

Edukt 2

HCID 2723981Borane;tetrahydrofuranHCID 22977458(2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

Produkt 1

HCID 20648576tert-Butyl (2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a THF (30 ml) solution of (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (3.77 g, 15 mmol) at 0° C., BH3.THF solution (1.0 M in THF, 45 ml) was added dropwise over 20 minutes. The reaction mixture was allowed to warm to room temperature and stirring was continued for a total of 16 hours. Reaction went to completion as monitored by LC-MS. The reaction mixture was quenched by the addition of saturated aqueous solution of NaHCO3 (60 ml) at room temperature and the stirring was continued at room temperature for 4 hours. Most THF was removed in vacuo and the mixture was extracted with EtOAc (˜60 ml), two layers were separated, organic layer was washed with brine (˜50 ml), repeat the extraction/wash cycle one more time. Organic layers were combined, dried (Na2SO4), filtered, solvent was removed in vacuo. Crude product was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 50:50). Compound (S)-tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate was obtained as a colorless oil: 2.6473 g (74% yield).

Aufarbeitung

  1. customwas continued for a total of 16 hours
  2. customReaction
  3. customThe reaction mixture was quenched by the addition of saturated aqueous solution of NaHCO3 (60 ml) at room temperature
  4. customMost THF was removed in vacuo
  5. extractionthe mixture was extracted with EtOAc (˜60 ml), two layers
  6. customwere separated
  7. washorganic layer was washed with brine (˜50 ml)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customsolvent was removed in vacuo
  11. customCrude product was purified by silica gel chromatography (Hexane/EtOAc, gradient from 100:0 to 50:50)

Quellen und Nachweise

ORD-Eintrag
ord-2dd26a04ed2a4fe8bcd42262b16d6ffe
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321763B2

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