Ammonium Chloride → (3R,6S)-6-(4-Allyldimethylsilylbenzyl)-3-isopropyl-2,5-diethoxy-3,6-dihydropyrazine

HRID 2228379Notes

Reaction equation

HRID 2228379 reaction equation
C([Li])CCC.[CH:6]([C@H:9]1[N:14]=[C:13]([O:15][CH2:16][CH3:17])[CH2:12][N:11]=[C:10]1[O:18][CH2:19][CH3:20])([CH3:8])[CH3:7].[CH2:21]([C:24]1[CH:34]=[CH:33][C:27]([CH:28](Br)[SiH:29]([CH3:31])[CH3:30])=[CH:26][CH:25]=1)[CH:22]=[CH2:23].[NH4+].[Cl-]>C1COCC1>[CH2:21]([C:24]1[CH:34]=[CH:33][C:27]([CH:28]([SiH:29]([CH3:30])[CH3:31])[C@H:12]2[N:11]=[C:10]([O:18][CH2:19][CH3:20])[C@@H:9]([CH:6]([CH3:7])[CH3:8])[N:14]=[C:13]2[O:15][CH2:16][CH3:17])=[CH:26][CH:25]=1)[CH:22]=[CH2:23]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 5325957(2R)-3,6-diethoxy-2-(propan-2-yl)-2,5-dihydropyrazineHCID 1317233674-Allyldimethylsilylbenzyl bromideHCID 178418339Butyllithium

Product 1

HCID 131723373(3R,6S)-6-(4-Allyldimethylsilylbenzyl)-3-isopropyl-2,5-diethoxy-3,6-dihydropyrazineYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (10.2 mL, 1.6 M solution in hexanes, 16.5 mmol) was injected into a solution of (3R)-3-isopropyl-2,5-diethoxy-3,6-dihydropyrazine (3.5 g, 16.5 mmol) in THF (70 mL) at −78° C. After 30 min of further stirring, 4-allyldimethylsilylbenzyl bromide (1 Scheme 2, 4.4 g, 16.5 mmol) in dry THF (30 mL) was added to the reaction mixture over a period of 1 h. After 1 h, saturated NH4Cl (1 mL) was added and the reaction mixture was allowed to warm to room temperature. The reaction mixture was concentrated, diluted with ethyl acetate (100 mL), and extracted with brine (20 mL×2). The organic layer was concentrated and the residue was purified by column chromatography (1:25 ethyl acetate/hexanes) to afford a colorless oil (4.7 g, 71%); 1H NMR (300 MHz, CDCl3) δ 0.28 (s; 6 H), 0.65 (d, J=6.75 Hz, 3 H), 0.96 (d, J=6.75 Hz, 3 H), 1.29 (t, J=7.05 Hz, 3 H), 1.35 (t) J=7.09 Hz, 3 H), 1.74 (d, J=8.05 Hz, 2 H), 2.19 (quintet of d, J=6.87, 3.21 Hz, 1 H), 3.10 (d, J=4.92 Hz, 2 H), 3.28 (m, 1 H), 4.07-4.24 (4 H), 4.31 (app q, J=4.50 Hz, 1 H), 4.83 (s, 1 H), 4.87 (m, 1 H), 5.77 (ddt, J=15.87, 11.13, 8.08 Hz, 1 H), 7.14 (d, J=7.98 Hz, 2 H), 7.38 (d, J=7.98 Hz, 2 H); 13C NMR (75 MHz, CDCl3) −3.4 −3.3, 14.5, 16.6, 19.1, 23.9, 31.3, 40.2, 56.7, 60.2, 60.4, 60.5, 113.3, 129.5 (2C), 133.2 (2C), 134.7, 135.9, 138.5, 162.2, 163.5; HRMS calcd for C23H36N2O2Si 400.2546, found 400.2543.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate (100 mL)
  3. extractionextracted with brine (20 mL×2)
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified by column chromatography (1:25 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5c29cf888b314e2a97ae49a5fbdd6fdb
Source dataset
uspto-grants-2002_07
Patent number
US06416861B1

Reaction notes

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