Triethylamine → [2-(2,3-Dihydro-indol-1-yl)-2-oxo-ethyl]-phosphonic acid diethyl ester

HRID 376451Notes

Reaction equation

HRID 376451 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][P:10]([CH2:15][C:16]([OH:18])=O)([O:12][CH2:13][CH3:14])=[O:11])[CH3:8].[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1.C(N(CC)CC)C>C1C=CC=CC=1.C1COCC1.CN(C)C=O>[CH2:13]([O:12][P:10]([CH2:15][C:16]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)=[O:18])(=[O:11])[O:9][CH2:7][CH3:8])[CH3:14]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10328IndolineHCID 36704(Diethoxyphosphinyl)acetic acidHCID 65578Oxalyl chloride

Product 1

HCID 54322212[2-(2,3-Dihydro-indol-1-yl)-2-oxo-ethyl]-phosphonic acid diethyl esterYield 66.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

Oxalyl chloride (5.96 mL, 68.3 mmol, 1.05 equiv) was added to a solution of diethylphosphonoacetic acid (12.8 g, 65.0 mmol, 1 equiv) and N,N-dimethylformamide (0.03 mL, 0.39 mmol, 0.006 equiv) in benzene (150 mL) at 23° C. The reaction mixture was stirred at 23° C. for 1 hour and then concentrated under reduced pressure. The resulting oil was dissolved in THF (30 mL) and added via cannula to a solution of indoline (7.38 g, 61.9 mmol, 0.95 equiv) and triethylamine (10.9 mL, 78.0 mmol, 1.2 equiv) in THF (200 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes, and it then was partitioned between 0.5 M HCl (150 mL) and EtOAc (2×150 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford a tan solid. Recrystallization from Et2O provided [2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-phosphonic acid diethyl ester (12.2 g, 63%) as a light brown solid: mp: 97-99° C.; R.function. =0.06 (50% EtOAc in hexanes); IR (cm-1) 3460, 1657, 1597, 1482; 1H NMR (CDCl3) δ 1.35 (t, 6H, J=7.2), 3.14 (d, 2H, J=22.4), 3.22 (d, 2H, J=8.4), 4.15-4.30 (m, 6H), 7.04 (t, 1H, J=7.0), 7.17-7.28 (m, 2H), 8.21 (d, 1H, J=9.0); Anal. (C14H20NO4P) C, H, N.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting oil was dissolved in THF (30 mL)
  3. stirringThe reaction mixture was stirred at 0° C. for 15 minutes
  4. customit then was partitioned between 0.5 M HCl (150 mL) and EtOAc (2×150 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a tan solid
  8. customRecrystallization from Et2O

Sources & evidence

ORD record
ord-a8720f23e3d142548f4292de7f50c80f
Source dataset
uspto-grants-2000_02
Patent number
US06020371

Reaction notes

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