Lithium Hydroxide → N-(2,2-Diphenyl-ethyl)-2-hydroxy-N-methyl-2-phenyl-acetamide

HRID 1064528Notes

Reaction equation

HRID 1064528 reaction equation
[C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][NH:9][CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([ClH][C:21](=[O:30])[CH:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[OH:23])(=O)C.C(N(CC)CC)C.[OH-].[Li+]>C(Cl)(Cl)Cl.O1CCCC1.CO>[C:11]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][N:9]([CH3:10])[C:21](=[O:30])[CH:22]([OH:23])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 12914583N-Methyl-2,2-diphenylethan-1-amine

Product 1

HCID 22174856N-(2,2-Diphenyl-ethyl)-2-hydroxy-N-methyl-2-phenyl-acetamideYield 93.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred solution of (2,2-diphenylethyl)methylamine (4.97 g, 23.5 mmol) in chloroform (50 mL) was added O-acetylmandelic chloride (5.3 mL, 24 mmol) followed by triethylamine (4.0 mL, 29 mmol). The reaction was stirred for 1 hour and then concentrated. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic layer was dried (sodium sulfate) and concentrated to afford a colorless gum. The crude amide was taken up in 1:1 tetrahydrofuran/methanol (80 mL) and treated with 1 N aqueous lithium hydroxide (30 mL, 30 mmol). The mixture was stirred for 2 hours and concentrated to remove the organic solvents. The remaining aqueous solution was diluted with water and extracted twice with ethyl acetate and once with methylene chloride. The combined organic extracts were dried (sodium sulfate) and concentrated to afford an off-white solid. This material was triturated with diethyl ether to afford 7.59 g (93%) of product as a white solid: 1H NMR (CDCl3) δ 7.43-6.98 (m, 15H), 5.07 (s, 1H), 4.57-4.44 (m, 1H), 4.36-4.28 (m, 1H), 3.76-3.64 (m, 1H), 2.46 (s, 3H) ppm.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate solution
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. concentrationconcentrated
  5. customto afford a colorless gum
  6. stirringThe mixture was stirred for 2 hours
  7. concentrationconcentrated
  8. customto remove the organic solvents
  9. additionThe remaining aqueous solution was diluted with water
  10. extractionextracted twice with ethyl acetate and once with methylene chloride
  11. dry with materialThe combined organic extracts were dried (sodium sulfate)
  12. concentrationconcentrated
  13. customto afford an off-white solid
  14. customThis material was triturated with diethyl ether

Sources & evidence

ORD record
ord-88f33495c92c4b379abd340d5509069a
Source dataset
uspto-grants-2005_11
Patent number
US06969728B2

Reaction notes

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