Sodium Carbonate → Ethyl 2-[4-(2-amino-[6-heptenyl]ethyl) phenoxy]-2-methylpropionate

HRID 377735Notes

Reaction equation

HRID 377735 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:18]=[CH:17][C:7]([O:8][C:9]([CH3:16])([CH3:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:5]=1.[CH:19](=O)[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH2:25].C([BH3-])#N.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[NH2:1][CH:2]([CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH:20]=[CH2:19])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]([CH3:15])([CH3:16])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 52833206-HeptenalHCID 19356632Ethyl 2-[4-(2-aminoethyl)-phenoxy]-2-methylpropionate2×

Product 1

HCID 57141758Ethyl 2-[4-(2-amino-[6-heptenyl]ethyl) phenoxy]-2-methylpropionateYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1.2 g of ethyl 2-[4-(2-aminoethyl)phenoxy]-2-methylpropionate [WO 92/10468, example 2, intermediate (c)] was dissolved in THF (20 mL). Hept6-enal (0.43 g) and 4A sieves (0.6 g ) were added. After 10 minutes, 0.25 g of sodium cyanoborohydride was added and the mixture stirred at room temperature for 50 minutes. The reaction mixture was poured into 5% aq. sodium carbonate and extracted with ethyl acetate. The organic extract was washed with brine, dried over MgSO4 and concentrated. Purification by flash chromatography (5-10% MeOH/CH2Cl2) gave 0.15 g of ethyl 2-[4-(2-amino-[6-heptenyl]ethyl) phenoxy]-2-methylpropionate as a light brown viscous oil. This material was dissolved in CH2Cl2 (5 mL) and 4-fluorophenylisocyanate (0.05 mL) was added. The solution was stirred at rt for 3 hours and then concentrated. Purification by flash chromatography gave 0.08 g of ethyl 2-(4-[2-(3-[4-fluorophenyl]-1-[6-heptenyl]ureido) ethyl]phenoxy)-2-methylpropionate as a yellow solid. This material was dissolved in EtOH (3 mL) and 1M aq. NaOH (1.5 mL), and the solution was heated at reflux for 30 min. The solution was concentrated, poured into 1N HCl and extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated to a yellow solid. Recrystallization fron ether/hexane gave 0.05 g of 2-(4-[2-(3-[4-fluorophenyl]-1-[6-heptenyl]ureido)ethyl]phenoxy)-2- methylpropionic acid as a white powder; m.p. 143-5 degC.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash chromatography (5-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a678df23dc5547d7ae8d68edcbead68d
Source dataset
uspto-grants-2000_02
Patent number
US06028109

Reaction notes

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