Hydrochloric Acid → {4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine dihydrochloride

HRID 272858ノート

反応式

HRID 272858 の反応式
[H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]1([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([C:28]#[N:29])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1.[OH-].[Na+].[ClH:32]>CCOCC.C(Cl)Cl.O1CCOCC1>[ClH:32].[ClH:32].[N:7]1([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([CH2:28][NH2:29])[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 598373944-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbonitrile

生成物 1

HCID 69216184{4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine dihydrochloride収率 81%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒2 回HCID 21881112Ethyl ether methylene chloride溶媒2 回

反応条件

温度
7.5 °C

実験手順

To a stirred suspension of LiAlH4 (1.81 g, 47.7 mmol, 5 eq) in Et2O/DCM (1:1, 30 mL) at 0 to 5° C. under a nitrogen atmosphere was added 4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonitrile (3 g, 9.55 mmol) in Et2O/DCM (1:1, 30 mL) over 15 minutes maintaining the temperature at 5 to 10° C. The reaction mixture was allowed to warm up to ambient temperature and stirred until complete. Sodium hydroxide (2N, 15 mL) was added dropwise and the resulting solids were filtered, washed with Et2O/DCM (1:1, 6×50 mL) and concentrated in vacuo at 40° C. A portion of the crude product from the above reaction (0.5 g, 1.57 mmol) was dissolved in dioxane (5 mL) and 4M HCl in dioxane (1.18 mL) added under N2. The reaction was stirred for 3 hours and filtered under a blanket of N2 (hygroscopic), washed with TBME and dried in the oven at 40° C. to give the title compound as a white solid (0.5 g, 81%). 1H NMR (400 MHz, DMSO-d6) δ11.24 (br s, 1H), 8.00 (br s, 3H), 7.33 (d, 2H), 6.98 (d, 2H), 4.08 (t, 2H), 3.76-3.63 (m, 2H), 3.60-3.46 (m, 2H), 3.45-3.18 (m, 4H), 3.07-2.87 (m, 4H), 2.25-1.77 (m, 10H).

後処理

  1. temperatureto warm up to ambient temperature
  2. filtrationthe resulting solids were filtered
  3. washwashed with Et2O/DCM (1:1, 6×50 mL)
  4. concentrationconcentrated in vacuo at 40° C
  5. customA portion of the crude product from the above reaction (0.5 g, 1.57 mmol)
  6. stirringThe reaction was stirred for 3 hours
  7. filtrationfiltered under a blanket of N2 (hygroscopic)
  8. washwashed with TBME
  9. customdried in the oven at 40° C.

出典と根拠

ORDレコード
ord-00bcfd331d834ae1b4546a3511c2835d
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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