Methyl phosphonic dichloride → tert-Butyl 4-(2-methyl-2-oxido-1,3,2-dioxaphosphinan-5-yl)benzoate

HRID 1013539

反応式

HRID 1013539 の反応式
[OH:1][CH2:2][CH:3]([C:6]1[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[CH:8][CH:7]=1)[CH2:4][OH:5].[CH3:19][P:20](Cl)(Cl)=[O:21]>C(Cl)Cl.O>[CH3:19][P:20]1(=[O:21])[O:5][CH2:4][CH:3]([C:6]2[CH:18]=[CH:17][C:9]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])=[CH:8][CH:7]=2)[CH2:2][O:1]1

参加物

5

反応物 2

HCID 12671Methyl phosphonic dichlorideHCID 57925849Tert-butyl 4-[2-hydroxy-1-(hydroxymethyl)ethyl]benzoate

生成物 1

HCID 57925899tert-Butyl 4-(2-methyl-2-oxido-1,3,2-dioxaphosphinan-5-yl)benzoate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

tert-Butyl 4-[2-hydroxy-1-(hydroxymethyl)ethyl]benzoate (440 mg, 1.74 mmol) and TEA (510 μl, 3.66 mmol) were taken up in CH2Cl2 (20 mL) and cooled to 0° C. Methylphosphonic dichloride (193 μl, 2.09 mmol) in CH2Cl2 (10 mL) was added dropwise over 30 minutes. The reaction was then allowed to warm to room temperature and stirred for 1 h. The mixture was diluted with water and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. Flash chromatography (0-10% MeOH/CH2Cl2) allowed separation of residual starting material from the diastereomeric products, but the diastereomers coeluted. Flash chromatography of the mixed diastereomers with 25-100% EtOAc/hexanes slowly eluted the first diastereomer, and the same column was flushed with 2-10% MeOH/CH2Cl2 to push off the second diastereomer (both were obtained as colorless solids). 1H NMR (CDCl3, 600 MHz) Diastereomer 1: δ 7.95 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 4.70-4.65 (m, 2H), 4.24-4.17 (m, 2H), 3.54-3.47 (m, 1H), 1.63 (d, J=18.0 Hz, 3H), 1.56 (s, 9H). Diastereomer 2: δ 7.97 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.3 Hz, 2H), 4.66-4.59 (m, 2H), 4.36-4.30 (m, 2H), 3.50-3.45 (m, 1H), 1.62 (d, J=17-3 Hz, 3H), 1.57 (s, 9H). MS: cal'd 313 (MH+), exp 313 (MH+).

後処理

  1. temperatureto warm to room temperature
  2. extractionextracted with CH2Cl2 (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customseparation
  7. washFlash chromatography of the mixed diastereomers with 25-100% EtOAc/hexanes slowly eluted the first diastereomer
  8. customthe same column was flushed with 2-10% MeOH/CH2Cl2
  9. customboth were obtained as colorless solids)

出典と根拠

ORDレコード
ord-8892f492ae3c43fe8ee2899144b4703a
出典データセット
uspto-grants-2011_07
特許番号
US07981874B2

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