Acetonitrile → 2-[4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl]-propan-1-ol

HRID 9736

反応式

HRID 9736 の反応式
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([N:11]([CH2:19][CH2:20]OS(C)(=O)=O)[CH2:12][CH2:13]OS(C)(=O)=O)[C:5]=2[O:4][CH2:3][CH2:2]1.[Br-].[Li+].[C:28](=[O:31])([O-])[O-].[K+].[K+].[C:34](#[N:36])[CH3:35]>>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:12][CH2:13][N:36]([CH:34]([CH3:35])[CH2:28][OH:31])[CH2:20][CH2:19]3)[C:5]=2[O:4][CH2:3][CH2:2]1

参加物

5

反応物 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 82050Lithium BromideHCID 11383877Methanesulfonic Acid 2-[(2,3-dihydro-benzo[1,4]dioxin-5-yl)-(2-methanesulfonyloxy-ethyl)-amino]-ethyl ester

生成物 1

HCID 101716032-[4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl]-propan-1-ol

反応条件

温度
82 °C

実験手順

Dimesylate III (67.0 g, 0.17 mol), D-alaminol (14.0 g, 0.19 mol), lithium bromide (31.0 g, 0.35 mol), and potassium carbonate (74.8 g, 0.54 mol) are mixed together with acetonitrile (750 mL). The resulting suspension is refluxed (82° C.) for 27 h with monitoring by HPLC. The reaction mixture is cooled, filtered, and insoluble residue washed with acetonitrile. Mother liquor is concentrated to a small volume, filtered through 200 cm3 of silica gel, and eluted with 1.5 L of MeOH 10% in EtOAc. After removing solvent on rotary evaporator, the residue is redissolved in EtOAc (200 mL). This solution is washed with water (2×50 mL), dried with MgSO4 and concentrated to produce IV as thick golden oil that slowly crystallizes upon standing; yield 29.4 g (63%) and purity 88.3 area % (LC-MS). Melting point=91–92° C. 1H NMR (CDCl3) δ 6.78 (t, J=7.5 Hz, 1H), 6.55 (m, 2H), 4.29 (m, 4H), 3.45 (dd, J=11, 5 Hz, 1H), 3.38 (t, J=11 Hz, 1H), 3.10 (br m, 4H), 2.86 (m, 3H), 2.63 (m, 2H), 0.96 (d, J=7.5 Hz, 3H).

後処理

  1. temperatureThe reaction mixture is cooled
  2. filtrationfiltered
  3. washinsoluble residue washed with acetonitrile
  4. concentrationMother liquor is concentrated to a small volume
  5. filtrationfiltered through 200 cm3 of silica gel
  6. washeluted with 1.5 L of MeOH 10% in EtOAc
  7. customAfter removing solvent
  8. customon rotary evaporator
  9. dissolutionthe residue is redissolved in EtOAc (200 mL)
  10. washThis solution is washed with water (2×50 mL)
  11. dry with materialdried with MgSO4
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-571c3a84051c458eaa66f8ab65574112
出典データセット
uspto-grants-2006_08
特許番号
US07091349B2

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