Phenol → (2S)-2-[2-oxo-4-(phenoxymethyl)-1-pyrrolidinyl]butanamide

HRID 1663573Notes

Reaction equation

HRID 1663573 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1.[C:15]1(O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:14]=[C:5]1[CH2:4][CH:3]([CH2:2][O:1][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:7][N:6]1[C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10]

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 60105803(2S)-2-[4-(hydroxymethyl)2-oxo-1-pyrrolidinyl]butanamide

Product 1

HCID 60105796(2S)-2-[2-oxo-4-(phenoxymethyl)-1-pyrrolidinyl]butanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a 50 ml three necked flask fitted with magnetic stirrer and dropping funnel under inert atmosphere, 1 g (5 mmoles, 1 eq) of (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanamide 6 is dissolved in 20 ml of THF and cooled down to 0° C. 517 mg of phenol, 0.87 ml (960 mg) of diethyl azodicarboxylate and 1.44 g of triphenylphosphine (5.5 mmoles, 1.1 eq each) are successively added and the mixture stirred for 2 hours. The mixture is concentrated to dryness and purified by Prep LC (500 kg SiO2, CH2Cl2/EtOH, 97.5:2.5) to give 1.1 g of pure 18, 80%, crystallised from ethyl acetate.

Workup

  1. concentrationThe mixture is concentrated to dryness
  2. custompurified by Prep LC (500 kg SiO2, CH2Cl2/EtOH, 97.5:2.5)
  3. customto give 1.1 g of pure 18, 80%
  4. customcrystallised from ethyl acetate

Sources & evidence

ORD record
ord-f0809eb32c10470aaa9edc3615552d06
Source dataset
uspto-grants-2011_10
Patent number
US08034958B2

Reaction notes

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