Methanol → 1-[4-Methoxycarbonyl-2-(3-pentylamino)phenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one

HRID 1635558Notes

Reaction equation

HRID 1635558 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].[CH3:22][CH2:23][C:24](=O)[CH2:25][CH3:26].C([BH3-])#N.[Na+].CO>ClCCl.C(O)(=O)C>[CH3:11][O:10][C:8]([C:6]1[CH:5]=[CH:4][C:3]([N:12]2[C:16]([CH2:17][OH:18])([CH2:19][OH:20])[CH2:15][CH2:14][C:13]2=[O:21])=[C:2]([NH:1][CH:24]([CH2:25][CH3:26])[CH2:23][CH3:22])[CH:7]=1)=[O:9]

Participants

7

Reactant 4

HCID 887MethanolHCID 7288Ethyl ketone3×HCID 5003444Sodium cyanoborohydride3×HCID 105657101-(2-Amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one

Product 1

HCID 104990031-[4-Methoxycarbonyl-2-(3-pentylamino)phenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-oneYield 84.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(2-amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one (0.1 g, 0.34 mmol) from Example 6 in 1 mL of dichloromethane and 0.5 mL of acetic acid was treated with 3-pentanone (0.2 g, 2.3 mmol) and sodium cyanoborohydride (0.075 g, 1.2 mmol). The resulting mixture was stirred at ambient temperature for 6 h after which time additional 3-pentanone (0.2 g, 2.3 mmol), sodium cyanoborohydride (0.075 g, 1.2 mmol) and methanol (0.5 mL) were added and stirring continued for 12 h. A third portion of 3-pentanone (0.3. g, 3.4 mmol) and sodium cyanoborohydride (0.15 g, 2.3 mmol) was added and the stirring continued for an additional 16 h. The reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried and concentrated. The residue was purified by chromatography (silica gel; 5% ethanol in ether) to give 0.105 g (82%) of 1-[4-methoxycarbonyl-2-(3-pentylamino)phenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one as a white solid, mp 183-185° C.

Workup

  1. additionwere added
  2. waitthe stirring continued for an additional 16 h
  3. customThe reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution
  4. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  5. customThe combined organic extracts were dried
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (silica gel; 5% ethanol in ether)

Sources & evidence

ORD record
ord-45f644c746fb4882af52953c6ae6bad2
Source dataset
uspto-grants-2003_01
Patent number
US06509359B1

Reaction notes

Loading…