Ethyl bromoacetate → Ethyl 2-(((1S,2S)-2-(hydroxymethyl)cyclohexyl)((S)-1-phenylethyl)amino)acetate

HRID 2065933Notes

Reaction equation

HRID 2065933 reaction equation
[C:1]1([C@@H:7]([NH:9][C@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]2[CH2:16][OH:17])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[OH:17][CH2:16][C@H:11]1[CH2:12][CH2:13][CH2:14][CH2:15][C@@H:10]1[N:9]([C@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:8])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10340Sodium CarbonateHCID 53236025((1S,2S)-2-((S)-1-phenylethylamino)cyclohexyl)methanol

Product 1

HCID 58193953Ethyl 2-(((1S,2S)-2-(hydroxymethyl)cyclohexyl)((S)-1-phenylethyl)amino)acetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (1S,2S)-2-[(S)-1-phenylethyl amino]cyclohexyl)methanol (11) (339.1 g) dissolved in acetonitrile (2.2 L) was charged to a reactor followed by ethyl bromoacetate (12) (234.2 mL) and anhydrous sodium carbonate (224.2 g) under nitrogen. The contents were heated to reflux temperature for NLT 18 hours with vigorous agitation. Acetonitrile was distilled under vacuum to about 1 L volume, cooled to <30° C. and diluted with 0.75 L of heptanes and 1.0 L of water. The aqueous layer was separated and extracted with heptanes (2×0.75 L), and the combined organic layers were washed with water (0.75 L) followed by 0.75 L 3.5 M aqueous sodium chloride solution. The heptane layer was dried with anhydrous magnesium sulfate and concentrated under vacuum to afford 557.8 g of ethyl 2-((1S,2S)-2-(hydroxymethyl)cyclohexyl)((S)-1-phenylethyl)amino) acetate (13) as the major isomer.

Workup

  1. additionwas charged to a reactor
  2. temperatureThe contents were heated
  3. temperatureto reflux temperature for NLT 18 hours with vigorous agitation
  4. distillationAcetonitrile was distilled under vacuum to about 1 L volume
  5. temperaturecooled to <30° C.
  6. additiondiluted with 0.75 L of heptanes and 1.0 L of water
  7. customThe aqueous layer was separated
  8. extractionextracted with heptanes (2×0.75 L)
  9. washthe combined organic layers were washed with water (0.75 L)
  10. dry with materialThe heptane layer was dried with anhydrous magnesium sulfate
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-528d785fa7464f06a2e0450fcff0f9bc
Source dataset
uspto-grants-2012_10
Patent number
US08288565B2

Reaction notes

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