Methyl iodide → HCID 57794808, compound

HRID 2099282Notes

Reaction equation

HRID 2099282 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 57794757HCID 57794757, compound

Product 1

HCID 57794808HCID 57794808, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1,1-dimethylethyl [((1R,2R)-1-phenyl-2-{[(phenylmethyl)oxy]methyl}cyclopropyl)methyl]carbamate (7.5 g, 20.4 mmol), accessed via the method of 11B, and methyl iodide (14.4 g, 102.0 mmol, 5 eq) in 100 mL THF cooled to 0° C. was added 1M sodium bis(trimethylsilyl)amide in THF (30.6 mL, 30.6 mmol, 1.5 eq). The reaction mixture was stirred 8 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 with EtOAc/hexanes (1:4)) to give the title compound (3.1 g, 8.1 mmol, 40%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.34-7.18 (m, 10H), 4.36-4.27 (m, 2H), 3.67-3.45 (m, 1H), 3.26-3.13 (m, 2H), 3.07-2.99 (m, 1H), 2.77-2.62 (m, 3H), 1.39-0.80 (m, 12H). ES-LCMS m/z 404.2 (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, eluted with EtOAc/hexanes (1:4))

Sources & evidence

ORD record
ord-02151d4eb3564ef9bcc4bf63feb19495
Source dataset
uspto-grants-2009_08
Patent number
US07569579B2

Reaction notes

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