Water → (+)-2-(6-Methoxy-naphthalen-2-yl)-propionic acid 1-(3-cyclopropyl methoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-pyridin-4-yl)-ethyl ester

HRID 241320Notes

Reaction equation

HRID 241320 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:16]([OH:26])[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N:21]=[CH:20][C:19]=3[Cl:25])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:15])[F:14])[CH2:3][CH2:2]1.[CH3:27][O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[CH:35]=[C:34]([C@H:39]([CH3:43])[C:40](O)=[O:41])[CH:33]=[CH:32]2.Cl.C(N=C=NCCCN(C)C)C.O>CN(C=O)C.CN(C)C1C=CN=CC=1>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([CH:16]([O:26][C:40](=[O:41])[CH:39]([C:34]3[CH:33]=[CH:32][C:31]4[C:36](=[CH:37][CH:38]=[C:29]([O:28][CH3:27])[CH:30]=4)[CH:35]=3)[CH3:43])[CH2:17][C:18]3[C:19]([Cl:25])=[CH:20][N:21]=[CH:22][C:23]=3[Cl:24])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:14])[F:15])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 594437601-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-pyridin-4-yl)-ethanol

Product 1

HCID 67494397(+)-2-(6-Methoxy-naphthalen-2-yl)-propionic acid 1-(3-cyclopropyl methoxy-4-difluoromethoxy-phenyl)-2-(3,5-dichloro-pyridin-4-yl)-ethyl esterYield 92.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Compound (3) (12.0 g) was dissolved in DMF (100 ml) then (S)-2-(6-methoxy-naphthalen-2-yl)-propionic acid (7.5 g), 4-dimethylaminopyridine (3.6 g), and 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (5.7 g) was added. After stirring at rt for 4 hours, water (1000 ml) is added. The mixture was extracted with EtOAc (500 ml×2), the combined organic layers are dried over sodium sulphate, and the solvent was removed by evaporation under reduced pressure to afford 17.0 g of an oil which is crystallized from EtOH thus obtaining 11.5 g of the title compound as mixture of diastereomers (11) and (13),

Workup

  1. extractionThe mixture was extracted with EtOAc (500 ml×2)
  2. dry with materialthe combined organic layers are dried over sodium sulphate
  3. customthe solvent was removed by evaporation under reduced pressure

Sources & evidence

ORD record
ord-4e6e9f6096b342cf9a5d924216b1e160
Source dataset
uspto-grants-2014_02
Patent number
US08648204B2

Reaction notes

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