Dimethyl Sulfoxide → Tert-butyl 4-((4-formylpiperidin-1-yl)methyl)benzoate

HRID 534169

反応式

HRID 534169 の反応式
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:32]=[CH:31][C:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.C(N(CC)CC)C>ClCCl.O>[CH:12]([CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])=[CH:31][CH:32]=2)[CH2:15][CH2:14]1)=[O:11]

参加物

7

反応物 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68385465tert-Butyl 4-((4-(hydroxymethyl)piperidin-1-yl)methyl)benzoate

生成物 1

HCID 86708240Tert-butyl 4-((4-formylpiperidin-1-yl)methyl)benzoate収率 55.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

反応条件

温度
-60 °C

実験手順

To a solution of oxalyl chloride (0.408 mL, 4.67 mmol) in dichloromethane (5 mL) at −60° C. was added a solution of DMSO (0.508 mL, 7.15 mmol) in 15 mL of dichloromethane over 30 minutes. The reaction was stirred for 30 minutes at −60° C. A solution of tert-butyl 4((4-(hydroxymethyl)piperidin-1-yl)methyl)benzoate (950 mg, 3.11 mmol) in 5 mL of dichloromethane was added over 10 minutes at −60° C. The reaction mixture was stirred for 3 hours at −60° C., then triethylamine (2.168 mL, 15.55 mmol) was added and after 10 minutes 10 mL of water was added. The reaction mixture was allowed to warm up to the room temperature. The layers were separated. The pH of the water layer was adjusted to ˜7 with 1 M HCl and then extracted with 20 mL of dichloromethane. The combined organic layers were washed with water and brine, then dried over MgSO, filtered and evaporated. The resulting oil was purified on a silica column eluting with EtOAc to yield tert-butyl 4-((4-formylpiperidin-1-yl)methyl)benzoate (550 mg, 1.722 mmol, 55.4% yield) as a yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 9.67 (d, J=1.26 Hz, 1H), 7.96 (d, J=8.34 Hz, 2H), 7.38 (d, J=8.34 Hz, 2H), 3.56 (s, 2H), 2.75-2.92 (m, 2H), 2.21-2.35 (m, 1H), 2.14 (t, J=10.48 Hz, 2H), 1.91 (dd, J=2.78, 13.14 Hz, 2H), 1.65-1.81 (m, 2H), 1.58-1.64 (m, 9H); LC-MS Rt=0.69 min; MS (ESI): 304.2 [M+H]+, 322.2 [M+H2O]+, 336.6 [M+Na]+

後処理

  1. stirringThe reaction mixture was stirred for 3 hours at −60° C.
  2. additionwas added
  3. temperatureto warm up to the room temperature
  4. customThe layers were separated
  5. extractionextracted with 20 mL of dichloromethane
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over MgSO
  8. filtrationfiltered
  9. customevaporated
  10. customThe resulting oil was purified on a silica column
  11. washeluting with EtOAc

出典と根拠

ORDレコード
ord-8cd65abbd571446a9786ca7e9f07b58d
出典データセット
uspto-grants-2014_10
特許番号
US08853408B2

関連ノート

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