Triethylamine → N-[[6-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]-N-methylglycine, Methyl Ester

HRID 1088543Notes

Reaction equation

HRID 1088543 reaction equation
[OH:1]N1C2C=CC=CC=2N=N1.[CH3:11][N:12]([CH3:21])[CH2:13][CH2:14][CH2:15]N=C=NCC.[CH3:22][O:23][C:24]1[C:25]([C:43]([F:46])([F:45])[F:44])=[C:26]2[C:31](=[CH:32][CH:33]=1)[C:30](C(O)=O)=[C:29]([O:37][CH2:38][C:39]([F:42])([F:41])[F:40])C=C2.Cl.N(C[C:51]([O:53][CH3:54])=[O:52])C.C(N(CC)CC)C>CN(C=O)C.O>[CH3:22][O:23][C:24]1[C:25]([C:43]([F:44])([F:45])[F:46])=[C:26]2[C:15](=[CH:32][CH:33]=1)[C:14]([C:13]([N:12]([CH3:11])[CH2:21][C:51]([O:53][CH3:54])=[O:52])=[O:1])=[C:29]([O:37][CH2:38][C:39]([F:40])([F:41])[F:42])[CH:30]=[CH:31]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 156149586-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)naphthoic acid

Product 1

HCID 14836049N-[[6-Methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]-N-methylglycine, Methyl EsterYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1-Hydroxybenzotriazole (5.05 g, 1.5 eq) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (5.74 g, 1.2 eq) were added to a stirred solution of 6-methoxy-2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)naphthoic acid, prepared by the process of Example 14 (9.18 g, 24.9 mmol) in anhydrous DMF (90 mL) at room temperature under a dry nitrogen atmosphere. After 11/4 hours, a suspension of methyl sarcosinate hydrochloride (6.96 g, 2.0 eq) in anhydrous DMF (40 mL) was added to the reaction followed by triethylamine (11.12 mL, 3.2 eq). After 30 minutes, the reaction was diluted with water (1.5 L) and extracted with ether (3×250 mL). The extracts were combined, dried with magnesium sulfate, and the ether was removed. The crude product was flash chromatographed (13:7→1:1 petroleum ether:ethyl acetate, silica) to provide the product as a clear oil (9.15 g, 81%). A small sample was triturated in petroleum ether to provide a white solid for analysis, m.p. 91.5°-93° C.

Workup

  1. additionwas added to the reaction
  2. extractionextracted with ether (3×250 mL)
  3. dry with materialdried with magnesium sulfate
  4. customthe ether was removed
  5. customchromatographed (13:7→1:1 petroleum ether:ethyl acetate, silica)

Sources & evidence

ORD record
ord-99e891fa06cb46d49f9fe9e62ee0261b
Source dataset
uspto-grants-1990_10
Patent number
US04962224

Reaction notes

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