4-Heptanone → 1-[2-(4-Heptylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one

HRID 1635561Notes

Reaction equation

HRID 1635561 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][CH2:24][C:25](=O)[CH2:26][CH2:27][CH3:28].C([BH3-])#N.[Na+]>ClCCl.C(O)(=O)C>[CH3:22][CH2:23][CH2:24][CH:25]([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])[CH2:26][CH2:27][CH3:28]

Participants

6

Reactant 3

HCID 312464-Heptanone2×HCID 5003444Sodium cyanoborohydride2×HCID 105657101-(2-Amino-4-methoxycarbonylphenyl)-5,5-bis-hydroxymethylpyrrolidin-2-one

Product 1

HCID 120183111-[2-(4-Heptylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-oneYield 75%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 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 0.3 mL of acetic acid was treated with 4-heptanone (0.175 g, 1.53 mmol) and sodium cyanoborohydride (0.05 g, 0.8 mmol). The resulting mixture was stirred at ambient temperature for 12 h after which time addition 4-heptanone (0.175 g, 1.53 mmol), sodium cyanoborohydride (0.05 g, 0.8 mmol) and acetic acid (0.3 mL) were added. Stirring was continued for 12 h. The reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution and the mixture was extracted with ethyl acetic (3×50 mL). The combined extracts were dried and concentrated. The residue was purified by chromatography (silica gel; 5% ethanol in ether) to give 0.15 g (75%) of 1-[2-(4-heptylamino)-4-methoxycarbonylphenyl]-5,5-bis-(hydroxymethyl)pyrrolidin-2-one as a white solid, mp 139-140° C.

Workup

  1. additionwere added
  2. stirringStirring
  3. waitwas continued for 12 h
  4. customThe reaction mixture was quenched with 10 mL of a saturated sodium bicarbonate solution
  5. extractionthe mixture was extracted with ethyl acetic (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-80d5cc46550b469e91c51377fdfebf13
Source dataset
uspto-grants-2003_01
Patent number
US06509359B1

Reaction notes

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