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Product Details of Dibenzyl N,N-diisopropylphosphoramidite

CAS No. :108549-23-1
Formula : C20H28NO2P
M.W : 345.42
SMILES Code : CC(N(C(C)C)P(OCC1=CC=CC=C1)OCC2=CC=CC=C2)C
MDL No. :MFCD00191988
InChI Key :ANPWLBTUUNFQIO-UHFFFAOYSA-N
Pubchem ID :196621

Safety of Dibenzyl N,N-diisopropylphosphoramidite

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Dibenzyl N,N-diisopropylphosphoramidite

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 108549-23-1 ]

[ 108549-23-1 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 873054-44-5 ]
  • [ 108549-23-1 ]
  • C38H41N2O5P [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole; In dichloromethane; acetonitrile; at 20℃; for 2h; Example 1 [5-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-2,4-ditert-butyl-phenoxy]phosphonic acid dibenzyl ester Tetrazole (0.45 M solution in CH3CN, 1.24 mL, 0.56 mmol) was added to a mixture of N-(5-hydroxy-2,4-ditert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (78 mg, 0.2 mmol) and dibenzyl diisopropylphosphoramidite (184 muL, 0.56 mmol) in dichloromethane (2 mL) and the reaction was stirred at room temperature for 2 h, then tert-butyl hydroperoxide (5.5M solution in decane, 102 muL, 0.56 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and saturated NaHCO3 solution. The organic layer was washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (silica gel, 50-100% ethyl acetate-hexanes) to yield [5-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-2,4-ditert-butyl-phenoxy]phosphonic acid dibenzyl ester as a clear oil (80 mg, 61%). 1H-NMR (400 MHz, d-DMSO) delta 13.04 (br s, 1H), 12.05 (s, 1H), 8.91 (s, 1H), 8.35 (dd, J=8.1, 1.0 Hz, 1H), 7.88 (s, 1H), 7.82 (m, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.53 (m, 1H), 7.37-7.31 (m, 11H), 5.19 (m, 4H), 1.44 (s, 9H), 1.33 (s, 9H); HPLC ret. time 3.77 min, 30-99% CH3CN, 5 min run; ESI-MS 653.4 m/z [M+H]+.
  • 2
  • [ 108549-23-1 ]
  • [ 1277151-44-6 ]
  • 3
  • [ 108549-23-1 ]
  • [ 108149-63-9 ]
  • [ 1415820-89-1 ]
YieldReaction ConditionsOperation in experiment
With 1H-tetrazole; In acetonitrile; for 1h; Scheme 21Dibenzyl diisopropylphosphoramidite (1.067 mL, 3.24 mmol) is added to te/ -butyl (4S)-4- (hydroxymethyl)-2,2-dimethyl-1 ,3-oxazolidine-3-carboxylate (0.5 g, 2.162 mmol) (106) [prepared from D-serine as described for the enantiomer in Organic Syntheses, Coll. Vol. 10, p. 320 (2004) and Vol. 77, p. 64 (2000)] and 1H-tetrazole (0.454 g, 6.49 mmol) in CH3CN (10 mL) and the mixture stirred for 1 h. The solvent is evaporated and the residue flash chromatographed (EtOAc-hexanes, 1 :9 v/v) to give tert-butyl (4R)-4- ([bis(benzyloxy)phosphanyl]oxy}methyl)-2,2-dimethyl-1 ,3-oxazolidine-3-carboxylate as a colourless oil. This is dissolved in CH2CI2 (10 mL) cooled in ice-water and MCPBA (m- chloroperoxybenzoic acid) (0.995 g, 4.32 mmol) added and stirred for 30 min. The mixture is diluted with CH2CI2 (50 mL) and washed with sat. aq. Na2S03, sat. aq. NaHC03 (3x) then brine, dried and the solvent evaporated. The residue is flash chromatographed (DCM-hexanes-EtOAc, 4:3:1 v/v/v) to give terf-butyl (4R)-4- ([bis(benzyloxy)phosphoryl]oxy}methyl)-2,2-dimethyl-1 ,3-oxazolidine-3-carboxylate(107) as a colourless oil (0.816 g, 77%). [a]^2 +21.5 (c 0.57, CHCI3). 1H NMR (500 MHz, CDCI3) 7.34 (s, 10H), 5.08-5.00 (m, 4H), 4.22-4.16 (m, 0.5H), 4.13-4.06 (m, 1 H), 3.97- 3.83 (m, 3H), 3.77 (q, J = 8.6, 0.5H), 1.52-1.41 (m, 15H). 13C NMR (125.7 MHz) 152.1 , 151.4 (C), 135.7 (C), 128.6 (CH), 127.9 (CH), 94.1 , 93.6 (C), 80.6, 80.3 (C), 69.4 (CH2j, 65.7, 65.3 (CH2), 64.8, 64.6 (CH2), 56.6, 56.5, 56.32, 56.26 (CH), 28.3 (CH3), 27.4, 24.3 (CH3), 26.6, 23.0 (CH3). Referenced to the centre line of CDCI3 at delta 77.0. 31 P NMR (202.3 MHz, CDCI3) -1.0 (s), -1.1 (s). ESI-HRMS for C25H34NNa07P [M+Na]+ calcd 514.1971 ; found 514.1968. The NMR spectra indicated (107) is a ~1 :1 mixture of conformational isomers.
With 1H-tetrazole; In acetonitrile; for 1h; Dibenzyl diisopropylphosphoramidite (1.067 mL, 3.24 mmol) is added to compound 8540,41 (0.5 g, 2.162 mmol) and 1H-tetrazole (0.454 g, 6.49 mmol) in CH3CN (10 mL) and the mixture stirred for 1 h. The solvent is evaporated and the residue flash chromatographed (EtOAc-hexanes, 1:9 v/v) to give tert-butyl (4R)-4-([bis(benzyloxy)phosphanyl]oxy}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate as a colourless oil. This is dissolved in CH2Cl2 (10 mL) cooled in ice-water and MCPBA (m-chloroperoxybenzoic acid) (0.995 g, 4.32 mmol) added and stirred for 30 min. The mixture is diluted with CH2Cl2 (50 mL) and washed with satd aq Na2SO3, satd aq NaHCO3 (3*) then brine, dried and the solvent evaporated. The residue is flash chromatographed (DCM-hexanes-EtOAc, 4:3:1 v/v/v) to give tert-butyl (4R)-4-([bis(benzyloxy)phosphoryl]oxy}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate as a colourless oil (0.816 g, 77%). [alpha]22D +21.5 (c 0.57, CHCl3). 1H NMR (500 MHz, CDCl3) 7.34 (s, 10H), 5.08-5.00 (m, 4H), 4.22-4.16 (m, 0.5H), 4.13-4.06 (m, 1H), 3.97-3.83 (m, 3H), 3.77 (q, J = 8.6, 0.5H), 1.52-1.41 (m, 15H). 13C NMR (125.7 MHz) 152.1, 151.4 (C), 135.7 (C), 128.6 (CH), 127.9 (CH), 94.1, 93.6 (C), 80.6, 80.3 (C), 69.4 (CH2), 65.7, 65.3 (CH2), 64.8, 64.6 (CH2), 56.6, 56.5, 56.32, 56.26 (CH), 28.3 (CH3), 27.4, 24.3 (CH3), 26.6, 23.0 (CH3). Referenced to the centre line of CDCl3 at delta 77.0. 31P NMR (202.3 MHz, CDCl3) -1.0 (s), -1.1 (s). ESI-HRMS for C25H34NNaO7P [M+Na]+ calcd 514.1971; found 514.1968. This material (0.77 g, 1.567 mmol) and 10% Pd-C (100 mg) are stirred in EtOH (15 mL) under a hydrogen atmosphere at ambient temperature and pressure for 16 h. The mixture is filtered through cellulose paper and the solvent is evaporated to give [(4R)-3-[(tert-butoxy)carbonyl]-2,2-dimethyl-1,3-oxazolidin-4-yl]methoxy}phosphonic acid as a colourless gum (480 mg). This is dissolved in 80% aq TFA (10 mL) and left at room temperature for 2 h. The solvent is evaporated and the residue dissolved in H2O (10 mL) and washed with CH2Cl2 (2 * 10 mL) then evaporated. The residue is dissolved in H2O and chromatographed on RP 18 silica gel (H2O) to give 86 as a colourless gum which solidified (0.26 g, 97%). [alpha]22D 0 (c 0.565, H2O). No measurable rotation observed. 1H NMR (500 MHz, D2O) 4.19-4.12 (m, 1H), 4.11-4.03 (m, 1H), 3.90 (dd, J = 12.3, 4.7, 1H), 3.81 (dd, J = 12.3, 6.7, 1H), 3.63 (m, 1H). Referenced to HOD at delta 4.79. 13C NMR (125.7 MHz, D2O) 62.9 (d, J = 3.2, CH2), 59.1 (CH2), 53.5 (d, J = 7.4, CH). Referenced to internal CH3CN at delta delta 1.47. 31P NMR (202.3 MHz, D2O) 0.0 (s). ESI-HRMS for C3H9NO5P [M-H]- calcd 170.0218; found 170.0211.
  • 4
  • [ 108549-23-1 ]
  • [ 198904-31-3 ]
  • methyl ((5S,8S,9S,14S)-8-benzyl-9-((bis(benzyloxy)phosphoryl)-oxy)-5-(tert-butyl)-15,15-dimethyl-3,6,13-trioxo-11-(4-(pyridin-2-yl)benzyl)-2-oxa-4,7,11,12-tetraazahexadecan-14-yl)carbamate [ No CAS ]
  • 5
  • [ 33689-29-1 ]
  • [ 108549-23-1 ]
  • methyl 1-((bis(benzyloxy)phosphoryl)oxy)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
70.1% A mixture of methyl l-hydroxycyclopropanecarboxylate (1.1 g, 9.47 mmol), dibenzyl N A-diisopropylphosphoramidite (4.77 mL, 14.21 mmol) and 1 //-tetrazole (0.45 M in acetonitrile) (31.6 mL, 14.21 mmol) was stirred at room temperatue for 8 h. The reaction was cooled to 0 C. was added hydrogen peroxide (0.581 mL, 18.95 mmol). The mixture was partitioned between ethyl acetate (100 mL) and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude material was purified by CombiFlash (silica gel 60-120 mesh; 30% ethyl acetate in hexane as eluent) to get methyl 1 -((/v.s(benzyloxy)phosphoryl)oxy) cyclopropanecarboxylate (2.5 g, 6.64 mmol, 70.1%) as a colorless oil. NMR (400 MHz, chloroform-^ d = 7.41 - 7.30 (m, 10H), 5.17 - 5.05 (m, 4H), 3.71 (s, 3H), 1.48 - 1.31 (m, 4H); LCMS (ES): m/z 378.0 [M + H]+.
 

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