Chloromethyl Methyl Ether → tert-butyl [(1R,2R)-2-(methoxymethoxy)-2,3-dihydro-1H-inden-1-yl](methoxymethyl)carbamate

HRID 64433Notes

Reaction equation

HRID 64433 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C@@H:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][C@H:9]1[OH:17])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)N[Si](C)(C)C.[K].C1(C)C=CC=CC=1.[CH3:36][O:37][CH2:38]Cl.[Cl-].[NH4+].C1[CH2:46][O:45][CH2:44]C1>C(OCC)(=O)C>[CH3:36][O:37][CH2:38][O:17][C@@H:9]1[CH2:10][C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@H:8]1[N:7]([CH2:44][O:45][CH3:46])[C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 7864Chloromethyl Methyl Ether2×HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 17998892(1R,2R)-N-Boc-1-amino-2-indanolHCID 131731101Potassium hexamethyldisilazane toluene2×

Product 1

HCID 86713447tert-butyl [(1R,2R)-2-(methoxymethoxy)-2,3-dihydro-1H-inden-1-yl](methoxymethyl)carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1 g of tert-butyl[(1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamate in 10 ml of THF was added 16.9 ml of a 0.5 M potassium hexamethyldisilazane/toluene solution at −78° C., followed by stirring for 30 minutes. 0.92 ml of chlorodimethyl ether was added thereto at −78° C., followed by warming to room temperature for 3 hours. 4 ml of a 0.5 M potassium hexamethyldisilazane/toluene solution and 0.31 ml of chlorodimethyl ether were added thereto at −78° C., followed by stirring at room temperature for 2 hours. To the reaction mixture were added a saturated aqueous ammonium chloride solution and ethyl acetate to carry out a layer separation operation. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 311 mg of tert-butyl [(1R,2R)-2-(methoxymethoxy)-2,3-dihydro-1H-inden-1-yl](methoxymethyl)carbamate.

Workup

  1. customat −78° C.
  2. customat −78° C.
  3. stirringby stirring at room temperature for 2 hours
  4. customa layer separation operation
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-78309252670e4d6fbe8ce6f3f33345cd
Source dataset
uspto-grants-2016_09
Patent number
US09447090B2

Reaction notes

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