Benzyl Bromide → tert-butyl(2S)-2-{4-[(benzyloxy)methyl]-2-oxo-1-pyrrolidinyl}butanoate

HRID 453258Notes

Reaction equation

HRID 453258 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:18][CH3:19])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:7](=[O:20])[CH2:6]1.[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[CH2:21]([O:3][CH2:4][CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:18][CH3:19])[C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[C:7](=[O:20])[CH2:6]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 57478730tert-butyl(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanoate

Product 1

HCID 57478746tert-butyl(2S)-2-{4-[(benzyloxy)methyl]-2-oxo-1-pyrrolidinyl}butanoateYield 37.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

In a 100 ml 3 necked flask, fitted with magnetic stirrer and reflux condenser under inert atmosphere, 1.1 g (60%, 27.5 mmoles, 1.1 eq) of sodium hydride are suspended in 60 ml of DMF and the mixture cooled down to 0° C. 6.37 g (24.8 mmoles, 1 eq) of tert-butyl(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanoate 398 in 10 ml of DMF are added cautiously. After 10 min, 3.3 ml (4.75 g, 27.8 mmoles, 1 eq) of benzyl bromide in 10 ml of DMF are added, and stirring continued for 30 min at 0° C., followed by 3 hours at room temperature. The mixture is concentrated to dryness, the residue is suspended in brine/CH2Cl2, decanted and extracted with CH2Cl2. The combined organic phases are dried over MgSO4, concentrated to dryness and the residue is purified by Prep LC (1 kg SiO2, hexane/MTBE, 40:60→0:100) to give 3.2 g of a mixture of t-Bu and Benzyl esters in two fractions, 37% total yields. It is used as such for the next step 7.3.1.b. 1H NMR (250 MHz, (CDCl3): 0.85 (t, 3H), 1.44 (s, 9H), 1.55-1.95 (m, 2H), 2.10 (dd, 1H), 2.45 (dd, 1H), 2.55-2.70 (m, 1H), 3.45-3.55 (m, 1H), 4.40 (dd, 1H), 4.55 (s, 2H), 7.20-7.40 (m, 5H).

Workup

  1. waitcontinued for 30 min at 0° C.
  2. waitfollowed by 3 hours at room temperature
  3. concentrationThe mixture is concentrated to dryness
  4. customdecanted
  5. extractionextracted with CH2Cl2
  6. dry with materialThe combined organic phases are dried over MgSO4
  7. concentrationconcentrated to dryness
  8. customthe residue is purified by Prep LC (1 kg SiO2, hexane/MTBE, 40:60→0:100)

Sources & evidence

ORD record
ord-5badc41e8fb946898a5ec1f819f9a449
Source dataset
uspto-grants-2013_07
Patent number
US08492416B2

Reaction notes

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