Chloromethyl Methyl Ether → HCID 66618049, compound

HRID 2200306Notes

Reaction equation

HRID 2200306 reaction equation
[CH:1]1([CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH2:3][CH2:2]1.[Li]CCCC.Cl[CH2:19][O:20][CH3:21]>C1COCC1>[CH:1]1([CH2:4][N:5]([CH2:19][O:20][CH3:21])[C:6](=[O:12])[O:7][C:8]([CH3:9])([CH3:11])[CH3:10])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 49757579tert-butyl N-(cyclopropylmethyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 66618049HCID 66618049, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Tert-butyl cyclopropylmethylcarbamate (11.2 g, 65.4 mmol) was dissolved into THF (60 mL) and set to stir at −78° C. BuLi (2.5M, 28.8 mL) was then added portionwise over 10 minutes. The reaction was allowed to stir while warming to −20° C. for 10 minutes, and continued stirring at that temperature for another 10 minutes. The reaction was then recooled to −78° C. at which point chloro(methoxy)methane (5.79 g, 72.0 mmol) was added via syringe. The reaction was then allowed to stir overnight with warming. The reaction was then quenched with 1N HCl and the organic layer separated. The aquoues layer was then extracted with DCM (2×), and the combined organic portions were dried with MgSO4, filtered and concentrated. The crude material was purified by passing through a silica plug eluting 10:1 Hex/EtOAc to give tert-butyl cyclopropylmethyl(methoxymethyl)carbamate (12.8 g, 91%) as a clear liquid.

Workup

  1. stirringto stir
  2. temperaturewhile warming to −20° C. for 10 minutes
  3. stirringcontinued stirring at that temperature for another 10 minutes
  4. additionwas added via syringe
  5. stirringto stir overnight
  6. temperaturewith warming
  7. customThe reaction was then quenched with 1N HCl
  8. customthe organic layer separated
  9. extractionThe aquoues layer was then extracted with DCM (2×)
  10. dry with materialthe combined organic portions were dried with MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude material was purified
  14. washeluting 10:1 Hex/EtOAc

Sources & evidence

ORD record
ord-f0d65ab495384c59b99dfc2cab34b457
Source dataset
uspto-grants-2016_06
Patent number
US09359340B2

Reaction notes

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