Chloromethyl Methyl Ether → Tert-butyl 2,4-dimethoxybenzyl(methoxymethyl)carbamate

HRID 82386Notes

Reaction equation

HRID 82386 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10].C([Li])CCC.Cl[CH2:26][O:27][CH3:28]>C1COCC1>[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]([CH2:26][O:27][CH3:28])[C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 63788699tert-butyl N-[(2,4-dimethoxyphenyl)methyl]carbamateHCID 178418339Butyllithium

Product 1

HCID 66618166Tert-butyl 2,4-dimethoxybenzyl(methoxymethyl)carbamateYield 104.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

tert-Butyl 2,4-dimethoxybenzylcarbamate (3.96 g, 14.8 mmol) was dissolved in THF (74 mL) and cooled to −78° C. Butyl lithium (7.44 mL, 16.3 mmol) was added dropwise to the solution over a five minute period to afford a pale-yellow solution. The solution was allowed to stir for 15 minutes before chloro(methoxy)methane (1.35 mL, 17.8 mmol) was added dropwise (neat). The reaction was stirred at −78° for 10 minutes and allowed to warm slowly to ambient temperature overnight. The reaction was concentrated in vacuo to afford a yellow gel, which was partitioned between half-saturated NH4Cl solution and ether. The aqueous portion was extracted once, and the organics were combined. The organic portion was washed with water, then brine, separated, dried over Na2SO4, filtered, and concentrated in vacuo. 1H NMR supports the desired near-pure (>90%) tert-butyl 2,4-dimethoxybenzyl(methoxymethyl)carbamate (4.81 g, 104% yield) as a pale-yellow oil which was used without purification.

Workup

  1. customto afford a pale-yellow solution
  2. additionwas added dropwise (neat)
  3. temperatureto warm slowly to ambient temperature overnight
  4. concentrationThe reaction was concentrated in vacuo
  5. customto afford a yellow gel, which
  6. customwas partitioned between half-saturated NH4Cl solution and ether
  7. extractionThe aqueous portion was extracted once
  8. washThe organic portion was washed with water
  9. custombrine, separated
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e098cece232444339ac94928753b10d7
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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