Sodium hydride → trans-N-Boc-4-(4-bromo-benzyloxy)-L-proline

HRID 49968

Reaktionsgleichung

Reaktionsgleichung von HRID 49968
N1CCC[C@H]1C(O)=O.[H-].[Na+].C[O:12][C:13](=[O:27])[C@@H:14]1[CH2:18][C@@H:17]([OH:19])[CH2:16][N:15]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].[Br:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=1>C1COCC1.O>[C:20]([N:15]1[CH2:16][C@H:17]([O:19][CH2:33][C:32]2[CH:35]=[CH:36][C:29]([Br:28])=[CH:30][CH:31]=2)[CH2:18][C@H:14]1[C:13]([OH:12])=[O:27])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 685274-Bromobenzyl bromideHCID 145742L-ProlineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Produkt 1

HCID 21301025trans-N-Boc-4-(4-bromo-benzyloxy)-L-prolineAusbeute 30,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

The compound of formula (P5), wherein R′ is 4-Bromo and the bonds linking the benzyloxy and methyl ester groups (depicted in P5 as wavy bonds) define the trans, L-proline configuration (2S,4R) was prepared as follows. To a suspension of sodium hydride (60% in oil) (0.12 g) (1.5 eq.) in 5 mL of dry THF was added trans-N-Boc-4-hydroxy-L-proline methyl ester (0.5 g) in 5 mL of dry THF. The reaction mixture was stirred for 45 minutes and a solution of 4-bromobenzyl bromide (0.75 g) (1.5 eq.) in 5 mL of dry THF was added. The reaction mixture was refluxed for 3 hours. After cooling to RT, the reaction mixture was diluted with water and extracted with EtOAc. The aqueous layer was acidified and extracted with DCM. The combined organic extracts were washed with water, dried over MgSO4, and evaporated under reduced pressure to afford trans-N-Boc-4-(4-bromo-benzyloxy)-L-proline (0.25 g). NMR (CDCl3, 200 MHz): 7.47 (2H, d), 7.2 (2H, d), 4.50-4.30 (3H, m), 4.25-4.1 (1H, m), 3.75 (3H, s), 3.8-3.5 (2H, m), 2.5-2.3 (1H, m), 2.15-1.95 (1H, m), 1.5-1.35 (9H).

Aufarbeitung

  1. customwas prepared
  2. temperatureThe reaction mixture was refluxed for 3 hours
  3. extractionextracted with EtOAc
  4. extractionextracted with DCM
  5. washThe combined organic extracts were washed with water
  6. dry with materialdried over MgSO4
  7. customevaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-59fd0c8b41fd4daf9a19a813bf25f45f
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06710064B2

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