Diisopropylethylamine → HCID 21904440, compound

HRID 2181598Notes

Reaction equation

HRID 2181598 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:6]=[C:7]([CH:13]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(N(C(C)C)C(C)C)C.[CH:28]([N:31]([CH:39]([CH3:41])[CH3:40])[P:32](Cl)[O:33][CH2:34][CH2:35][C:36]#[N:37])([CH3:30])[CH3:29].C(OCC)(=O)C.CCCCCCC>ClCCl>[CH3:41][CH:39]([N:31]([P:32]([O:33][CH2:34][CH2:35][C:36]#[N:37])[O:1][CH2:2][C:3]1[CH:13]=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:6]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:4]=1)[CH:28]([CH3:29])[CH3:30])[CH3:40]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 610139Diethyl 5-(hydroxymethyl)isophthalateHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 21899848Ethylacetate heptane

Product 1

HCID 21904440HCID 21904440, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Protocol for preparing the diester phosphoramidite diethyl 5-[[[[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino]oxy]methyl]-1,3-benzenedicarboxylate: 1.29 g (5 mmol) of diethyl 5-(hydroxymethyl)isophthalate [252.27] (98%, Aldrich; CAS 181425-91-2) were dissolved in 20 ml of dry dichloromethane at room temperature and mixed with 2.59 g (40 mmol, 4 eq) of N-ethyldiisopropylamine [129.25] and 1.3 g (11 mmol, 1.1 eq) of 2-cyanoethyl N,N-diisopropylchlorophosphoramidite [236.68] (Aldrich; CAS 89992-70-1). After 15 min at room temperature, thin layer chromatography (ethyl acetate/n-heptane (1:4) showed completion of the reaction. The mixture was concentrated and mixed with 30 ml of ethyl acetate/n-heptane (2:3). The precipitated hydrochloride was removed by filtration. The filtrate was concentrated and applied directly to a chromatography column. Elution with ethyl acetate/n-heptane (1:4) gave 1.6 g (70%) of diethyl 5-[[[[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino]oxy]methyl]-1,3-benzenedicarboxylate as a colorless oil. C22H33N2O6P; 1H-NMR 8.59 (m, 1H, arom.), 8.21 (m, 2H, arom.), 4.87-4.75 (m, 2H, CH2 cyanoethyl), 4.41 (q, J=6.98 Hz, 4H, CH2 ethyl), 3.95-3.80 (m, 2H, 2×CH i-Pr), 3.74-3.61 (m, 2H, CH2 cyanoethyl), 2.66 (t, J (P,H)=6.45 Hz, 2H, O—CH2-arom), 1.41 (t, J=6H, 2×CH3 ethyl), 1.23-1.20 (m, 12H, CH3, i-Pr): 31P-NMR (CDCl3): δ 149.94; 13C-NMR (CDCl3): δ=165.8 (C═O), 140.2 (C—CH2—O—P), 132.1 (2×C arom.), 131.1 (2×C—H arom), 129.7 (C H arom), 117.6 (CN), 64.7 (P—O—CH2-arom), 61.4 (2×CH2 ethyl), 58.6 (O—CH2—CH2—CN), 43.4 (2×C—H i-Pr), 24.7 (4×CH3 i-Pr), 20.5 (O—CH2—CH2—CN), 14.4 (CH3 ethyl); HRMS 453.2156 ([M+H]+C22H34N2O6P calculated: 453.21545). Chromatographic purification and analytical characterization were carried out according to the protocols described above.

Workup

  1. customcompletion of the reaction
  2. concentrationThe mixture was concentrated
  3. additionmixed with 30 ml of ethyl acetate/n-heptane (2:3)
  4. customThe precipitated hydrochloride was removed by filtration
  5. concentrationThe filtrate was concentrated
  6. washElution with ethyl acetate/n-heptane (1:4)

Sources & evidence

ORD record
ord-365d00210a194a51973b7bc7206bcf45
Source dataset
uspto-grants-2005_05
Patent number
US06893822B2

Reaction notes

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