Acetic Acid → 5,5-Bis-(hydroxymethyl)-1-{4-methoxycarbonyl-2-[(3-pentyl)methylamino]phenyl}pyrrolidin-2-one

HRID 1635563Notes

Reaction equation

HRID 1635563 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[N:12]1[C:16]([CH2:19][OH:20])([CH2:17][OH:18])[CH2:15][CH2:14][C:13]1=[O:21].[C:22](O)(=O)C.[CH2:26]([CH:28]([CH2:31][CH3:32])C=O)[CH3:27].C([BH3-])#N.[Na+]>ClCCl>[OH:20][CH2:19][C:16]1([CH2:17][OH:18])[N:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=2[N:1]([CH:28]([CH2:31][CH3:32])[CH2:26][CH3:27])[CH3:22])[C:13](=[O:21])[CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 73592-EthylbutyraldehydeHCID 5003444Sodium cyanoborohydrideHCID 105657101-(2-Amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one

Product 1

HCID 700299065,5-Bis-(hydroxymethyl)-1-{4-methoxycarbonyl-2-[(3-pentyl)methylamino]phenyl}pyrrolidin-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 1-(2-amino-4-methoxycarbonylphenyl)-5,5-bis-(hydroxymethyl)pyrrolidin-2-one (0.1 g, 0.34 mmol) from Example 6 in 2 mL of dichloromethane was treated with acetic acid (0.1 g, 1.6 mmol), 2-ethylbutyraldehyde (0.065 g, 0.65 mmol) and sodium cyanoborohydride (0.035 g, 0.55 mmol). The resulting mixture was stirred at ambient temperature for 2 h. The reaction mixture was quenched with a saturated sodium bicarbonate solution (2 mL) and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic layers were dried and concentrated to give 0.14 g of crude oil which was purified by chromatography (silica gel; 10% ethanol in ether) to yield 0.115 g (90%) of 5,5-bis-(hydroxymethyl)-1-{4-methoxycarbonyl-2-[(3-pentyl)methylamino]phenyl}pyrrolidin-2-one as white solid, mp 142-143° C.

Workup

  1. customThe reaction mixture was quenched with a saturated sodium bicarbonate solution (2 mL)
  2. extractionthe mixture was extracted with ethyl acetate (3×25 mL)
  3. customThe combined organic layers were dried
  4. concentrationconcentrated
  5. customto give 0.14 g of crude oil which
  6. customwas purified by chromatography (silica gel; 10% ethanol in ether)

Sources & evidence

ORD record
ord-4528b20523984caa8fa73bdef7451ed1
Source dataset
uspto-grants-2003_01
Patent number
US06509359B1

Reaction notes

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