Chloromethyl Methyl Ether → HCID 86657785, compound

HRID 401920Notes

Reaction equation

HRID 401920 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[C@H:10]([OH:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.Cl[CH2:30][O:31][CH3:32]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[C@H:10]([O:19][CH2:30][O:31][CH3:32])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 86657783HCID 86657783, compound

Product 1

HCID 86657785HCID 86657785, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-cis-4-acetoxymethyl-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (45.0 mmol, 12.3 g) in anhydrous DCM (100 mL) at room temperature was added N,N-diisopropylethyl amine (180 mmol, 31.4 mL). The reaction mixture was cooled to 0° C. using an ice bath. To this was added chloromethylmethyl ether (135 mmol, 11.4 mL) dropwise over 15 minutes. After completion of addition, the reaction was stirred for 12 hours while coming to room temperature. All volatiles were removed under reduced pressure. The residue was dissolved in ethyl acetate (250 mL) and washed with water (3×50 mL) and brine (50 mL). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on 110 g SiO2 cartridge using ethyl acetate/hexanes gradient to give (±)-cis-4-acetoxymethyl-3-methoxymethoxy-piperidine-1-carboxylic acid tert-butyl ester (13.3 g).

Workup

  1. additionAfter completion of addition
  2. customwhile coming to room temperature
  3. customAll volatiles were removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (250 mL)
  5. washwashed with water (3×50 mL) and brine (50 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on 110 g SiO2 cartridge

Sources & evidence

ORD record
ord-8562da371f1642f79b80995228137971
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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