Nitrogen → 2-Methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid Methyl Ester

HRID 585270Notes

Reaction equation

HRID 585270 reaction equation
CN(N=O)C(N[N+]([O-])=O)=N.[OH-].[K+].N#N.[C:15](=O)=O.CC(C)=O.[CH3:22][C:23]([O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH2:27][C:28]1[S:29][CH:30]=[CH:31][CH:32]=1)[C:24]([OH:26])=[O:25]>C(Cl)Cl.CCOCC>[CH3:15][O:25][C:24](=[O:26])[C:23]([CH3:22])([O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:27][C:28]1[S:29][CH:30]=[CH:31][CH:32]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 14797Potassium HydroxideHCID 18522661Acetone cardiceHCID 223400602-Methyl-2-phenoxy-3-thiophen-2-yl-propionic AcidHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 208231582-Methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid Methyl EsterYield 28%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Procedure

In a 100 mL beaker, 1.12 g of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) was added to a solution of ether (30 mL) and 5 N KOH (2.3 mL) and stirred until N2 evolution ceased. In another beaker, crude 2-methyl-2-phenoxy-3-thiophen-2-yl-propionic acid (1.00 g) was dissolved in CH2Cl2 (20 mL). The beaker containing the ether/base mixture was then placed in a Dewar flask containing dry ice/acetone, the aqueous layer was frozen and the ether layer decanted into the other beaker containing the crude acid solution. This mixture was then stirred for an additional 5 min, which by HPLC showed the reaction to be complete. The solvent was removed in vacuo to provide a crude oil. Purification by flash chromatography EtOAc: hexane (1:10) provided 533 mg of desired product (28%): 1H NMR (400 MHz, CDCl3) • 7.16-7.22 (m, 4H), 6.96 (m, 1H), 6.91 (m, 1H), 6.84 (m, 2H), 3.73 (s, 3H), 3.49 (d, 1H), 3.38 (d, 1H), 1.42 (s, 3H); MS (EI) 277.1 (M+H)+.

Workup

  1. temperaturethe aqueous layer was frozen
  2. customthe ether layer decanted into the other beaker
  3. additioncontaining the crude acid solution
  4. customthe reaction
  5. customThe solvent was removed in vacuo
  6. customto provide a crude oil
  7. customPurification by flash chromatography EtOAc: hexane (1:10)

Sources & evidence

ORD record
ord-69c51cde82414d0bbe4c05bcee819080
Source dataset
uspto-grants-2005_08
Patent number
US06930120B2

Reaction notes

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