Ethanolamine → 2-((3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylamino)ethanol

HRID 1506519Notes

Reaction equation

HRID 1506519 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20](C=O)=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:30])([F:29])[F:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:31]([CH2:33][NH2:34])[OH:32].[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([BH3-])#N.[Na+]>O.ClCCCl>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH2:35][NH:34][CH2:33][CH2:31][OH:32])=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:29])([F:28])[F:30])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 866698753-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde

Product 1

HCID 671719312-((3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylamino)ethanolYield 61.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

A mixture of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 40 mg, 0.097 mmol), Ethanolamine (0.059 mL, 0.975 mmol), 1,2-dichloroethane (3 mL) and sodium triacetoxyborohydride (62.0 mg, 0.292 mmol) was stirred at room temperature overnight. Sodium cyanoborohydride (20 mg, 0.318 mmol) was then added. The mixture was stirred at room temperature for 1 h before water (1 mL) was added. The aqueous layer was extracted with ethyl acetate (3×1 mL). The combined organic solutions were concentrated under reduced pressure. Purification using reverse phase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, neutralization with saturated aqueous sodium bicarbonate solution, and extraction with ethyl acetate gave 2-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylamino)ethanol (28 mg, 0.060 mmol, 61.8% yield) as a white solid.

Workup

  1. additionwas added
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×1 mL)
  3. concentrationThe combined organic solutions were concentrated under reduced pressure
  4. customPurification
  5. concentrationphase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, neutralization
  6. extractionwith saturated aqueous sodium bicarbonate solution, and extraction with ethyl acetate

Sources & evidence

ORD record
ord-f93d0012d98b48cd93618e2de9413342
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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