Reaktion #40467

Reaktionsgleichung

N-benzyl-serine benzyl ester

Intermediate 16

N-benzyl-serine benzyl ester

3-bromo-2-methyl-propene

K2CO3

iodine

3-bromo-2-methyl-propene

→

4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester

Ausbeute 64.0%

Lösungsmittel

MeCN

EtOAc hexane

EtOAc hexane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture was stirred for another 15 hrs
2. 2
   workup.STIRRINGAfter 4 hrs of stirring
3. 3
   SonstigeThe reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml)
4. 4
   WaschenThe separated organic phase was washed successively with water, saturated NaHCO3 and brine
5. 5
   Trocknendried over MgSO4
6. 6
   Einengenconcentrated to dryness
7. 7
   SonstigeThe residue was purified on silica (5% EtOAc/Hexane)

Vorschrift

To a solution of N-benzyl-serine benzyl ester (Intermediate 16, 6.35 g) in 90 ml of MeCN at ambient temperature was added 3-bromo-2-methyl-propene (5.6 ml), KI (740 mg) and K2CO3 (7.7 g). The reaction mixture was stirred at ambient temperature for 72 hrs. 1 ml of 3-bromo-2-methyl-propene was added and the reaction mixture was stirred for another 15 hrs. Only a small amount of starting material remained based on TLC (1:1; EtOAc-hexane). To the resulting mixture was added 11.2 g of iodine. After 4 hrs of stirring, TLC (10% EtOAc/hexane) showed complete conversion. The reaction mixture was partitioned into ether (300 ml) and 0.5 M Na2S2O3 (100 ml). The separated organic phase was washed successively with water, saturated NaHCO3 and brine, dried over MgSO4, and concentrated to dryness. The residue was purified on silica (5% EtOAc/Hexane) to give 6.65 g (yellowish oil, 64% yield, about 4:1 mixture) of compound 4-benzyl-6-iodomethyl-6-methyl-morpholine-3-carboxylic acid benzyl ester. Major Component: 1H-NMR (300 MHz, CDCl3): δ 1.22 (s, 3H), 2.50 (d, 1H), 3.16-3.36 (m, 3H), 3.75-3.95 (m, 4H), 4.06 (dd, 1H), 5.16 (d, 1H), 5.21 (d, 1H), 7.28-7.36 (m, 10H).

Quelle