Methanol → 1-[2-(3-Hexylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one

HRID 1635560Notes

Reaction equation

HRID 1635560 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][CH2:26][CH3:27].C([BH3-])#N.[Na+].CO>ClCCl.C(O)(=O)C>[CH3:22][CH2:23][CH:24]([NH: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]([CH2:17][OH:18])([CH2:19][OH:20])[CH2:15][CH2:14][C:13]1=[O:21])[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 887MethanolHCID 115093-Hexanone3×HCID 5003444Sodium cyanoborohydride3×HCID 105657101-(2-Amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one

Product 1

HCID 120183091-[2-(3-Hexylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-oneYield 90.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(2-amino-4-methoxycarbonylphenyl)-5,5-bis-(hydroxymethyl)pyrrolidin-2-one (0.15 g, 0.51 mmol) from Example 6 in 1 mL of dichloromethane and 0.5 mL of acetic acid was treated with 3-hexanone (0.3 g, 3 mmol) and sodium cyanoborohydride (0.1 g, 1.6 mmol). The resulting mixture was stirred at ambient temperature for 6 h after which time additional 3-hexanone (0.1 g, 1 mmol), sodium cyanoborohydride (0.05 g, 0.8 mmol) and methanol (0.5 mL) were added. Stirring was continued for 12 h. A third portion of 3-hexanone (0.17 g, 1.7 mmol) and sodium cyanoborohydride (0.055 g, 0.9 mmol) was added and stirring continued for an additional 16 h. The reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution and extracted with ethyl acetate (3×50 mL). The combined extracts were dried and concentrated. The residue was purified by chromatography (silica gel; 5% ethanol in ether) to give 0.175 g (90%) of 1-[2-(3-hexylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one as an oil.

Workup

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

Sources & evidence

ORD record
ord-0e928ae78d3b4d7eb107ce2b6c327463
Source dataset
uspto-grants-2003_01
Patent number
US06509359B1

Reaction notes

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