Methyl iodide → HCID 57794797, compound

HRID 2099281Notes

Reaction equation

HRID 2099281 reaction equation
[C:1]1([C@:7]2([CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:9][C@H:8]2[CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CI.[CH3:30][Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[CH3:30][N:20]([CH2:19][C@@:7]1([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:9][C@H:8]1[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 57794783HCID 57794783, compound

Product 1

HCID 57794797HCID 57794797, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1,1-dimethylethyl [((1S,2R)-phenyl-2-{[(phenylmethyl)oxy]methyl}cyclopropyl)methyl]carbamate (39.2 g, 92 mmol), accessed via the method of 11A, and methyl iodide (39.2 g, 276 mmol, 3 eq) in 300 mL THF cooled to 0° C. was added 1M sodium bis(trimethylsilyl)amide in THF (138 mL, 138 mmol, 1.5 eq). The reaction mixture was stirred 2 h at 0° C. followed by 16 h at ambient temperature. The reaction mixture was partitioned between EtOAc and water, the phases separated, the aqueous phase extracted twice with EtOAc, the organic phases combined, washed with brine, dried over MgSO4, filtered and concentrated to an amber oil. The crude material was purified by flash chromatography (SiO2, eluted successively with DCM/hexanes (1:1), DCM, and EtOAc/hexanes (1:4)) to give the title compound (22.25 g, 58 mmol, 63%) as a pale yellow oil. ES-LCMS m/z 404.30(M+Na).

Workup

  1. waitfollowed by 16 h at ambient temperature
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. customthe phases separated
  4. extractionthe aqueous phase extracted twice with EtOAc
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to an amber oil
  9. customThe crude material was purified by flash chromatography (SiO2
  10. washeluted successively with DCM/hexanes (1:1), DCM, and EtOAc/hexanes (1:4))

Sources & evidence

ORD record
ord-f82abf2715a14eb690b20cee603266d2
Source dataset
uspto-grants-2009_08
Patent number
US07569579B2

Reaction notes

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