Methoxyacetyl chloride → N-{(1S,2S)-1-(3,5-Difluorobenzyl)-2-[(3R,5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-2-hydroxyethyl}-2-methoxyacetamide hydrochloride

HRID 20480Notes

Reaction equation

HRID 20480 reaction equation
[NH2:1][C@@H:2]([CH2:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=1)[C@@H:3]([CH:5]1[CH2:10][O:9][C@@H:8]([O:11][CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C@H:7]([CH3:17])[NH:6]1)[OH:4].[CH3:27][O:28][CH2:29][C:30]([Cl:32])=[O:31]>>[ClH:32].[F:26][C:21]1[CH:20]=[C:19]([CH:24]=[C:23]([F:25])[CH:22]=1)[CH2:18][C@H:2]([NH:1][C:30](=[O:31])[CH2:29][O:28][CH3:27])[C@@H:3]([C@H:5]1[CH2:10][O:9][C@@H:8]([O:11][CH2:12][C:13]([CH3:15])([CH3:16])[CH3:14])[C@H:7]([CH3:17])[NH:6]1)[OH:4]

Participants

3

Reactant 2

HCID 96623Methoxyacetyl chlorideHCID 68563960(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-[(5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-propan-1-ol

Product 1

HCID 68560724N-{(1S,2S)-1-(3,5-Difluorobenzyl)-2-[(3R,5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-2-hydroxyethyl}-2-methoxyacetamide hydrochlorideYield 65.1%

Conditions

Temperature
0 °C

Procedure

Dissolve (1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-[(5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-propan-1-ol (31 mg, 0.083 mmol) in dry 1:1 dichloromethane:diethyl ether (1 mL) under nitrogen. Cool to 0° C. and add dropwise methoxyacetyl chloride (7.6 μL, 0.083 mmol). Stir for 1 hour, quench with methanol, concentrate and purify (reverse-phase HPLC, eluting with 10:90 to 50:50 acetonitrile:water with 8 mM hydrochloric acid), to give the title compound (26 mg, 65%).

Workup

  1. dry with materialin dry 1:1 dichloromethane
  2. customquench with methanol
  3. concentrationconcentrate
  4. custompurify
  5. wash(reverse-phase HPLC, eluting with 10:90 to 50:50 acetonitrile:water with 8 mM hydrochloric acid)

Sources & evidence

ORD record
ord-84d190eff37442fc82171f1d461e91c1
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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