Tetrahydrofuran → (2R,5S)-3,6-Diethoxy-2-isopropyl-5-(2-[3-methoxy-4-(4-phenyl-butoxy)-phenyl]-ethyl)-2,5dihydro-pyrazine

HRID 2053461Notes

Reaction equation

HRID 2053461 reaction equation
[CH2:1]([O:3][C:4]1[C@@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=[C:7]([O:10][CH2:11][CH3:12])[CH2:8][N:9]=1)[CH3:2].[CH2:16]([Li])[CH2:17][CH2:18][CH3:19].[CH2:21]1[CH2:25][O:24][CH2:23][CH2:22]1>>[CH2:1]([O:3][C:4]1[C@@H:5]([CH:13]([CH3:15])[CH3:14])[N:6]=[C:7]([O:10][CH2:11][CH3:12])[C@H:8]([CH2:19][CH2:18][C:17]2[CH:16]=[CH:21][C:25]([O:24][CH2:23][CH2:22][CH2:16][CH2:17][C:18]3[CH:14]=[CH:13][CH:5]=[CH:4][CH:19]=3)=[C:7]([O:10][CH3:11])[CH:8]=2)[N:9]=1)[CH3:2]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 5325957(2R)-3,6-diethoxy-2-(propan-2-yl)-2,5-dihydropyrazineHCID 178418339Butyllithium

Product 1

HCID 59655577(2R,5S)-3,6-Diethoxy-2-isopropyl-5-(2-[3-methoxy-4-(4-phenyl-butoxy)-phenyl]-ethyl)-2,5dihydro-pyrazine

Procedure

To a solution of (R)-3,6-diethoxy-2-isopropyl-2,5-dihydro-pyrazine (2.2 g; 10.4 mmol; Lohr, Birgit et al., Synlett, 1999, 7, 1139-1141) in dry THF (30 ml) at −78° C. there is added n-butyllithium (6.5 ml; 10.4 mmol; 1.6M in n-hexane). After 30 minutes at −78° C. the endproduct of step b) (4.3 g; 10.4 mmol) dissolved in dry THF (15 ml) is added tropwise over a period of 10 minutes. The reaction mixture is allowed to warm up to RT and it is kept at RT for 20 hours. After quenching with saturated aqueous ammonium chloride solution and extraction (2 times) with ethyl acetate the organic phase is dried over MgSO4 and concentrated under reduced pressure. The crude is purified on silica gel using diethylether/n-hexane (1/9) as mobile phase.

Workup

  1. additionis added tropwise over a period of 10 minutes
  2. customAfter quenching with saturated aqueous ammonium chloride solution and extraction (2 times) with ethyl acetate the organic phase
  3. dry with materialis dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude is purified on silica gel

Sources & evidence

ORD record
ord-1ff7ad1a65714c399ebfbea68e6c7bb5
Source dataset
uspto-grants-2008_02
Patent number
US07326801B2

Reaction notes

Loading…