Triethylamine → 2-(1,2-Diphenyl-ethyl)-morpholine-4-carboxylic acid benzyl ester

HRID 736038Notes

Reaction equation

HRID 736038 reaction equation
[C:1]1([CH:7]([CH:15]2[O:20][CH2:19][CH2:18][NH:17][CH2:16]2)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30]>ClCCl>[CH2:32]([O:31][C:29]([N:17]1[CH2:18][CH2:19][O:20][CH:15]([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:16]1)=[O:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 111498202-(1,2-Diphenyl-ethyl)-morpholine

Product 1

HCID 578486362-(1,2-Diphenyl-ethyl)-morpholine-4-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(1,2-Diphenyl-ethyl)-morpholine (2 g, 7.49 mmol) in dry dichloromethane (15 ml) at 0° C. under nitrogen atmosphere is added neat triethylamine (2.2 ml, 15.5 mmol, 2.07 equiv.) followed by the addition of neat benzyl chloroformate (1.61 ml, 11.23 mmol, 1.5 equiv.). The reaction is left to reach room temperature over 24 hours and then quenched by addition of a saturated bicarbonate (NaHCO3) aqueous solution. The resulting mixture is extracted with dichloromethane and the resulting organic phases are mixed, dried (MgSO4) and concentrated under reduced pressure to give an oil containing the four possible diastereoisomers (2.3 g, 78%). The diastereoisomers are separated using preparative HPLC, followed by each single enantiomer being resolved by preparative chiral HPLC.

Workup

  1. waitThe reaction is left
  2. customquenched by addition of a saturated bicarbonate (NaHCO3) aqueous solution
  3. extractionThe resulting mixture is extracted with dichloromethane
  4. additionthe resulting organic phases are mixed
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give an oil
  8. additioncontaining the four possible diastereoisomers (2.3 g, 78%)
  9. customThe diastereoisomers are separated

Sources & evidence

ORD record
ord-e6c2da69357b4339931f4d4e73ec1a7f
Source dataset
uspto-grants-2009_09
Patent number
US07595315B2

Reaction notes

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