Methyl iodide → ((S)-1-methoxymethyl-3,3-dimethyl-butyl)-carbamic acid tert-butyl ester

HRID 1052138Notes

Reaction equation

HRID 1052138 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:18])[NH:9][C@H:10]([CH2:16][OH:17])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:6])([CH3:5])[CH3:4].IC.[C:21]([O-])(O)=O.[Na+]>C1COCC1>[C:3]([O:7][C:8](=[O:18])[NH:9][C@H:10]([CH2:16][O:17][CH3:21])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 58280489((S)-1-hydroxymethyl-3,3-dimethyl-butyl)-carbamic acid tert-butyl ester

Product 1

HCID 90019826((S)-1-methoxymethyl-3,3-dimethyl-butyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (51.3 mg, 1.284 mmol) in THF (10 mL) cooled at 0° C. under Argon atmosphere was slowly added ((S)-1-hydroxymethyl-3,3-dimethyl-butyl)-carbamic acid tert-butyl ester (300 mg, 1.167 mmol). The mixture was stirred at 0° C. for 30 min and iodomethane (0.095 ml, 1.517 mmol) was added. The reaction mixture was allowed to reach RT and further stirred overnight. To complete the reaction, NaH (24 mg, 0.584 mmol) was again added at 0° C. followed 30 min later by the addition of iodomethane (36 μL, 0.584 mmol). The reaction mixture was stirred at RT for 6 h, then poured into a sat. aq. solution of NaHCO3 and extracted twice with CH2Cl2. The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude material was purified by flash chromatography on silica gel (c-hexane to c-hexane/EtOAc 8:2) to give the desired material as a white powder. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 6.60 (m, 1H), 3.66 (m, 1H), 3.23 (s, 3H), 3.14 (m, 1H), 3.05 (m, 1H), 1.38 (s, 9H), 1.30 (m, 2H), 0.88 (s, 9H).

Workup

  1. waitto reach RT and further stirred overnight
  2. additionwas again added at 0° C.
  3. stirringThe reaction mixture was stirred at RT for 6 h
  4. extractionextracted twice with CH2Cl2
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by flash chromatography on silica gel (c-hexane to c-hexane/EtOAc 8:2)

Sources & evidence

ORD record
ord-910e203f470c4856bc303eaa8c65d3b7
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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