m-Chloroperbenzoic acid → tert-Butyl 3-(2-(2-((bis(benzyloxy)phosphoryl)oxy)ethoxy)ethoxy)-2,2-dimethylpropanoate

HRID 1507749Notes

Reaction equation

HRID 1507749 reaction equation
[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][C:9]([CH3:18])([CH3:17])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].CC1NN=NN=1.C(N(CC)[P:28]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)C.C1C=C(Cl)C=C(C(OO)=[O:55])C=1>C1COCC1.C(Cl)Cl>[CH2:38]([O:37][P:28]([O:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][C:9]([CH3:18])([CH3:17])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([O:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:55])[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

7

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 5066231Dibenzyl diethylphosphoramiditeHCID 117642669tert-Butyl 3-(2-(2-hydroxyethoxy)ethoxy)-2,2-dimethylpropanoateHCID 178434708HCID 178434708, compound

Product 1

HCID 117642919tert-Butyl 3-(2-(2-((bis(benzyloxy)phosphoryl)oxy)ethoxy)ethoxy)-2,2-dimethylpropanoateYield 89.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of tert-butyl 3-(2-(2-hydroxyethoxy)ethoxy)-2,2-dimethylpropanoate (49) (6.87 g, 26.2 mmol), 5-methyl-1H-tetrazole (4.40 g, 52.4 mmol), and dibenzyl diethylphosphoramidite (12.47 g, 39.3 mmol) in THF (66 mL) was allowed to stir at RT for 1.5 h. The solution was cooled to 0° C. and m-CPBA (10.85 g, 47.1 mmol) was slowly added, the mixture was allowed to stir at RT for 16 h. The reaction was diluted with DCM (200 mL) and washed with sat. NaHCO3 (aq.) (4×100 mL), the organic layer was dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (220 g, 0-40% EtOAc in isohexane) to afford tert-butyl 3-(2-(2-((bis(benzyloxy)phosphoryl)oxy)ethoxy)ethoxy)-2,2-dimethylpropanoate (50) (12.2 g, 89%) as a colourless oil: m/z 545 (M+Na)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.35-7.31 (m, 10H), 5.09-5.00 (m, 4H), 4.13-4.09 (m, 2H), 3.65-3.63 (m, 2H), 3.59-3.52 (m, 4H), 3.39 (s, 2H), 1.41 (s, 9H), 1.11 (s, 6H).

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. stirringto stir at RT for 16 h
  3. washwashed with sat. NaHCO3 (aq.) (4×100 mL)
  4. dry with materialthe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography (220 g, 0-40% EtOAc in isohexane)

Sources & evidence

ORD record
ord-0d166bd263dc4504be2d842e6646b2fe
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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