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Trifluoroacetic acid → 4-{(2S)-3-[7-(2-Aminoethyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]-2-hydroxypropoxy}benzonitrile

HRID 1992332
ノート
印刷プレビュー

反応式

HRID 1992332 の反応式
[C:1]([C:3]1[CH:32]=[CH:31][C:6]([O:7][CH2:8][C@@H:9]([OH:30])[CH2:10][N:11]2[CH2:18][CH:17]3[O:19][CH:13]([CH2:14][N:15]([CH2:20][CH2:21][NH:22]C(=O)OC(C)(C)C)[CH2:16]3)[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[NH2:22][CH2:21][CH2:20][N:15]1[CH2:16][CH:17]2[O:19][CH:13]([CH2:12][N:11]([CH2:10][C@H:9]([OH:30])[CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:32][CH:31]=3)[CH2:18]2)[CH2:14]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 9876235Azd 7009

生成物 1

HCID 685227854-{(2S)-3-[7-(2-Aminoethyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]-2-hydroxypropoxy}benzonitrile収率 70.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

tert-Butyl 2-{7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-di-azabicyclo[3.3.1]non-3-yl}ethylcarbamate (2.9 g, 6.56 mmol; see WO 01/28992) was dissolved in DCM (30 mL). Trifluoroacetic acid (22.2 g, 194.7 mmol) was added and the solution was stirred for 2 h. The mixture was concentrated under reduced pressure, redissolved in toluene and acetonitrile and concentrated in vacuo again. The product mixture was dissolved in acetonitrile (50 mL) and solid K2CO3 (9.7 g, 10.2 mmol) was added. The mixture was filtered and concentrated under reduced pressure. The mixture was then redissolved in a mixture of EtOAc and a saturated solution of NaHCO3. The mixture was extracted twice with DCM, the combined organic extracts dried (Na2SO4) and evaporated to afford 1.6 g (68.7%) of the title compound.

後処理

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionredissolved in toluene
  3. concentrationacetonitrile and concentrated in vacuo again
  4. dissolutionThe product mixture was dissolved in acetonitrile (50 mL)
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe mixture was then redissolved in a mixture of EtOAc
  8. extractionThe mixture was extracted twice with DCM
  9. dry with materialthe combined organic extracts dried (Na2SO4)
  10. customevaporated

出典と根拠

ORDレコード
ord-164213ce8bdf45d7915dff0fcae0f6ce
出典データセット
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07648985B2

反応ノート

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