Sodium Iodide → 7-Isopropyl-3-(4-fluorophenacyl)-3,7-diazabicyclo[3.3.1]nonane

HRID 129543

反応式

HRID 129543 の反応式
Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=[O:4].[Na+].[I-].[CH:14]([N:17]1[CH2:24][CH:23]2[CH2:25][CH:19]([CH2:20][NH:21][CH2:22]2)[CH2:18]1)([CH3:16])[CH3:15]>CC#N>[CH:14]([N:17]1[CH2:24][CH:23]2[CH2:25][CH:19]([CH2:20][N:21]([CH2:2][C:3]([C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)=[O:4])[CH2:22]2)[CH2:18]1)([CH3:16])[CH3:15]

参加物

5

反応物 3

HCID 5238Sodium IodideHCID 1202482-Chloro-4'-fluoroacetophenoneHCID 150358373-Isopropyl-3,7-diazabicyclo[3.3.1]nonane

生成物 1

HCID 152889497-Isopropyl-3-(4-fluorophenacyl)-3,7-diazabicyclo[3.3.1]nonane収率 86.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a standard setup was added 2-chloro-4'-fluoroacetophenone (7.55 g, 43.8 mmol) and NaI (9.85 g, 65.7 mmol) in H3CCN (30 ml) which was then heated for 30 minutes with stirrring. The solution was allowed to cool to room temperature (30 min) which was followed by dropwise addition of amine 105 (6.7 g, 39.8 mmol) to give a light yellow mixture which was stirred overnight. Filtration (suction) removed excess NaI and the filtrate was diluted with H2O and transferred to a separatory funnel. The resulting homogenous solution (pH~5) was extracted (ether, 3×75 ml) with the latter being discarded, and the pH of the aqueous layer was adjusted to 12 using 10% NaOH. Extraction (ether, 3×75 ml) of the aqueous layer was followed by another extraction (H2CCl2, 3×75 ml) and the ether extracts were discarded. The organic layer (H2CCl2) was dried (Na2SO4, 2 h), filtered, and concentrated (rotary evaporator) to give 2.9 g (86.1%) of amine 55 as a light yellow solid; mp 193°-194° C. IR (KBr) 3060, 3040 (Ar-H), 2940, 2805 (C-H), 1700 (C=O) cm-1 ; 1H NMR (DCCl3) d 1.45 (d, 6 H, CH3 isopropyl), 1.81 [d, 1 H, H(9)ax ], 2.11 [d, 1 H, H(9)eq ], 2.32 lbs, 2 H, H(1,5)], 2.85 (d, 2 H, ring protons), 3.37 (d, 2 H, ring protons), 3.49 (d, 2 H, ring protons), 3.86 (m, 3 H, ring protons, C-H isopropyl), 4.18 (s, 2 H, ArC(O)CH2), 7.15 (t, 2 H, Ar-H), 8.02 (m, 2 H, Ar-H); 13C NMR (DCCl3) ppm 17.01 (CH3 isopropyl), 28.04 [C(1,5)], 30.05 [C(9)], 53.74, 57.2257.34 (ring carbons, C-H isopropyl), 62.22 [ArC(O)CH2 ], 115.58, 115.88, 130.57, 130.70, 131.22, 131.26 (Ar-C), 164.10, 167.49 (J=265.8 Hz, ArC-F), 194.99 (C=O). Ketone 55 was slightly unstable, and thus was reduced to the corresponding alcohol 110.

後処理

  1. temperaturewas then heated for 30 minutes with stirrring
  2. customto give a light yellow mixture which
  3. filtrationFiltration (suction)
  4. customremoved excess NaI
  5. additionthe filtrate was diluted with H2O
  6. customtransferred to a separatory funnel
  7. extractionThe resulting homogenous solution (pH~5) was extracted (ether, 3×75 ml) with the
  8. extractionExtraction (ether, 3×75 ml) of the aqueous layer
  9. extractionwas followed by another extraction (H2CCl2, 3×75 ml)
  10. dry with materialThe organic layer (H2CCl2) was dried (Na2SO4, 2 h)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custom(rotary evaporator)

出典と根拠

ORDレコード
ord-d5303b9d963d4fd4bfa5d0c8043e32c3
出典データセット
uspto-grants-1995_11
特許番号
US05468858

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