Triethylamine → ((S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidin-2-yl)methyl methanesulfonate

HRID 633344Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 633344
[F:1][C:2]1([F:16])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([CH2:14][OH:15])[CH2:3]1.CCN(CC)CC.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>C(Cl)Cl>[CH3:24][S:25]([O:15][CH2:14][C@@H:4]1[CH2:3][C:2]([F:1])([F:16])[CH2:6][N:5]1[C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])(=[O:27])=[O:26]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 20648576tert-Butyl (2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Produkt 1

HCID 86704454((S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidin-2-yl)methyl methanesulfonate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a CH2Cl2 (22 ml) solution of (S)-tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate (2.65 g, 11.2 mmol) and Et3N (2.3 ml, 16.8 mmol), at 0° C., methylsulfonyl chloride (0.95 ml, 12.3 mmol) was added dropwise over ˜2 minutes, ice bath was removed after 15 minutes, and stirring was continued at room temperature for another 30 minutes. Reaction went to completion as monitored by LC-MS. The reaction mixture was cooled to 0° C. and was quenched by addition of saturated aqueous solution of NaHCO3 (˜30 ml), stifling was continued at 0° C. for 5 minutes and at room temperature for 15 minutes. Two layers were separated, aqueous layer was extracted with CH2Cl2 (˜30 ml). Organic layers were combined, washed with brine (˜25 ml), dried (Na2SO4), filtered, solvent was removed in vacuo. Compound ((S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidin-2-yl)methyl methanesulfonate was obtained as a very light yellow oil: 3.40 g (96% crude yield).

Aufarbeitung

  1. customice bath was removed after 15 minutes
  2. customReaction
  3. customwas quenched by addition of saturated aqueous solution of NaHCO3 (˜30 ml)
  4. waitstifling was continued at 0° C. for 5 minutes and at room temperature for 15 minutes
  5. customTwo layers were separated
  6. extractionaqueous layer was extracted with CH2Cl2 (˜30 ml)
  7. washwashed with brine (˜25 ml)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customsolvent was removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-cf1b22231f68415aa7f076ce160e8f0d
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321763B2

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