Ethanolamine → HCID 86663499, compound

HRID 1950715Notes

Reaction equation

HRID 1950715 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:28]([F:31])([F:30])[F:29])[O:14][N:13]=[C:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]([OH:27])=O)=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:63][CH2:64][CH2:65][OH:66]>CN(C=O)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:28]([F:30])([F:31])[F:29])[O:14][N:13]=[C:12]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:18]([C:25]([NH:63][CH2:64][CH2:65][OH:66])=[O:27])=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86663497HCID 86663497, compound

Product 1

HCID 86663499HCID 86663499, compoundYield 67.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid (Preparation 7, 1 g, 2.1 mmol) in DMF (35 mL) was added HATU (970 mg, 2.5 mmol) and triethylamine (1.0 mL, 7.0 mmol). The reaction was stirred at room temperature for 15 minutes then treated with 2-amino-ethanol (145 mg, 2.4 mmol). The reaction was stirred at room temperature for 2 hours. Next, the reaction was diluted with 0.1N NaOH and extracted with EtOAc (2×150 mL). The combined organic phase was dried (Na2SO4) and concentrated under vacuum. The crude material was chromatographed (80 g Redi-Sep column) eluting from 100% heptane to 40:60 EtOAc:heptane to afford the intermediate (734 mg, 67%) as a solid. 1HNMR (CDCl3) δ ppm: 8.82 (1H), 8.33 (1H), 7.76-7.60 (5H), 7.50 (1H), 6.51 (1H) 4.28 (1H), 3.94-3.83 (3H), 3.76 (2H), 2.35 (1H); m/z (Cl) 515 [M+H]+.

Workup

  1. stirringThe reaction was stirred at room temperature for 2 hours
  2. extractionextracted with EtOAc (2×150 mL)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. customThe crude material was chromatographed (80 g Redi-Sep column)
  6. washeluting from 100% heptane to 40:60 EtOAc

Sources & evidence

ORD record
ord-2bf5de94ce074d409bc1e41d9b2e1cbe
Source dataset
uspto-grants-2013_03
Patent number
US08404649B2

Reaction notes

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