Chloromethyl Methyl Ether → 5-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-methoxymethoxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane

HRID 514627Notes

Reaction equation

HRID 514627 reaction equation
[O:1]([CH2:19][C:20]1([CH2:28][N:29]2[CH:33]=[C:32]([CH2:34][OH:35])[N:31]=[C:30]2[N+:36]([O-:38])=[O:37])[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22][CH2:21]1)[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.[CH3:48][O:49][CH2:50]Cl.C(=O)(O)[O-].[Na+]>ClCCl>[O:1]([CH2:19][C:20]1([CH2:28][N:29]2[CH:33]=[C:32]([CH2:34][O:35][CH2:48][O:49][CH3:50])[N:31]=[C:30]2[N+:36]([O-:38])=[O:37])[CH2:25][O:24][C:23]([CH3:26])([CH3:27])[O:22][CH2:21]1)[Si:2]([C:15]([CH3:16])([CH3:18])[CH3:17])([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 903003915-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-hydroxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane

Product 1

HCID 903004155-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-methoxymethoxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxaneYield 78.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

101 mg (0.19 mmol equivalents) of 5-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-hydroxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane was dissolved in 2.0 mL of dichloromethane and cooled to about 0° C. in an ice bath. 125 μL (0.72 mmol equivalents) of N,N-diisopropylethylamine and 41 μL (0.51 mmol equivalents) of methoxymethyl chloride were added thereto, and the mixture was stirred for 26 hours while increasing the temperature to room temperature (25° C.). After completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added dropwise, and the mixture was extracted three times with ethyl acetate. The combined ethyl acetate layers were washed with water and brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum. The obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=2/1) to give 86 mg (0.15 mmol equivalents) of 5-(t-butyldiphenylsiloxymethyl)-2,2-dimethyl-5-[(4-methoxymethoxymethyl-2-nitro-1H-imidazol-1-yl)methyl]-1,3-dioxane.

Workup

  1. temperaturewhile increasing the temperature to room temperature (25° C.)
  2. customAfter completion of the reaction
  3. extractionthe mixture was extracted three times with ethyl acetate
  4. washThe combined ethyl acetate layers were washed with water and brine
  5. dry with materialdried with anhydrous magnesium sulfate
  6. concentrationsubsequently concentrated under vacuum
  7. customThe obtained crude product
  8. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=2/1)

Sources & evidence

ORD record
ord-04b2898aa35e460a83af6a7bc972eae7
Source dataset
uspto-grants-2015_08
Patent number
US09107964B2

Reaction notes

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