Sodium hydride → tert-Butyl 3-(2-(2-(benzyloxy)ethoxy)ethoxy)-2,2-dimethylpropanoate

HRID 1507747Notes

Reaction equation

HRID 1507747 reaction equation
[OH:1][CH2:2][C:3]([CH3:12])([CH3:11])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].CS(O[CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=O)=O.[H-].[Na+]>CN(C=O)C>[CH2:24]([O:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][O:1][CH2:2][C:3]([CH3:12])([CH3:11])[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 155254392-(2-(Benzyloxy)ethoxy)ethyl methanesulfonateHCID 54272639Tert-butyl 3-hydroxy-2,2-dimethylpropanoate

Product 1

HCID 117642942tert-Butyl 3-(2-(2-(benzyloxy)ethoxy)ethoxy)-2,2-dimethylpropanoateYield 96.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 3-hydroxy-2,2-dimethylpropanoate (353 mg, 2.03 mmol) and 2-(2-(benzyloxy)ethoxy)ethyl methanesulfonate (47) (500 mg, 1.82 mmol) in DMF (6 mL) at 0° C. was added NaH (60 wt % in oil) (109 mg, 2.73 mmol), and the reaction mixture was allowed to stir at RT for 30 min. The reaction mixture was quenched with sat. NH4Cl (aq.) (1 mL) diluted with water (20 mL) and washed with EtOAc (4×20 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (12 g, 0-40% Et2O in isohexane) to afford tert-butyl 3-(2-(2-(benzyloxy)ethoxy)ethoxy)-2,2-dimethylpropanoate (48) (619 mg, 96%) as a colourless oil: m/z 375 (M+Na)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.32-7.25 (m, 5H), 4.54 (s, 2H), 3.66-3.56 (m, 8H), 3.41 (s, 2H), 1.40 (s, 8H), 1.10 (s, 6H).

Workup

  1. customThe reaction mixture was quenched with sat. NH4Cl (aq.) (1 mL)
  2. additiondiluted with water (20 mL)
  3. washwashed with EtOAc (4×20 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography (12 g, 0-40% Et2O in isohexane)

Sources & evidence

ORD record
ord-79f417a846a24043aae65a2b792d7705
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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