tert-Butyldimethylsilyl chloride → (+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester

HRID 751159Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 751159
[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([OH:10])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].CCN(C(C)C)C(C)C.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([O:10][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12]

Komponenten

6

Edukt 3

HCID 28928tert-Butyldimethylsilyl chloride2×HCID 81531Diisopropylethylamine2×HCID 59754228rac-1-tert-butyl 2-methyl (2R,3S)-3-hydroxypiperidine-1,2-dicarboxylate

Produkt 1

HCID 68458695(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl esterAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 77C (3.3 g, 12.7 mmol) in DCM (50 mL) was added DIPEA (6.63 mL, 38.1 mmol), tert-butyldimethylsilyl chloride (3.83 g, 25.4 mmol, 2.0 equiv) and DMAP (310 mg, 5.24 mmol, 0.2 equiv). The resulting mixture was stirred at rt overnight. TLC showed no completion and therefore another 2.2 mL of DIPEA and 1.91 g of tert-butyldimethylsilyl chloride were added and stirred at rt for 3 days. The mixture was concentrated and the residue was diluted with EtOAc (100 mL), washed with 0.5 N HCl (2×30 mL), brine (2×30 mL), dried (MgSO4) and evaporated to give the crude product as a light pink oil. Purification of the crude product by flash chromatography (5-10% EtOAc/hexane) gave the desired product 77D (3.8 g, 81%): Rf (10% EtOAc/hexane) 0.25; HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.3 min (100%); MS (ES) m/z 374 [M+1]+.

Aufarbeitung

  1. stirringstirred at rt for 3 days
  2. concentrationThe mixture was concentrated
  3. additionthe residue was diluted with EtOAc (100 mL)
  4. washwashed with 0.5 N HCl (2×30 mL), brine (2×30 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give the crude product as a light pink oil
  8. customPurification of the crude product by flash chromatography (5-10% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-d4abe7f146a14cffb14f9b74c80d62bc
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07405234B2

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