Phenylpropanolamine → HCID 66607791, compound

HRID 1810360Notes

Reaction equation

HRID 1810360 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH:23]=O)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.[CH3:26][C@H:27]([NH2:36])[C@H:28]([OH:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(O)(=O)C.C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][C:14]=2[CH2:23][NH:36][C@@H:27]([CH3:26])[C@H:28]([OH:35])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1

Participants

8

Reactant 3

HCID 10297Phenylpropanolamine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86633167(2'-Formyl-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

Product 1

HCID 66607791HCID 66607791, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(2′-Formyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester (0.094 g, 0.27 mmol), (1R,2S)-(−)-norephedrine (0.054 g, 0.35 mmol), and sodium triacetoxyborohydride (0.113 g, 0.53 mmol) were combined in dichloroethane (1 mL). Acetic acid (1 drop) was added, and the reaction was stirred at room temperature for 40 minutes. Analytical tlc showed that only starting material was present, so the reaction was heated to 50° C. and stirred overnight. Analytical LCMS showed that some starting material was still present, so additional (1R,2S)-(−)-norephedrine (0.057 g, 0.38 mmol), and sodium triacetoxyborohydride (0.115 g, 0.53 mmol) were added, and the reaction was stirred for 3.5 hours at 50° C. After cooling to room temperature, the mixture was diluted with CH2Cl2 and saturated aqueous NaHCO3, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound.

Workup

  1. temperaturewas heated to 50° C.
  2. stirringstirred overnight
  3. stirringthe reaction was stirred for 3.5 hours at 50° C
  4. temperatureAfter cooling to room temperature
  5. extractionthe aqueous layer was extracted twice with CH2Cl2
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ff730c5afff2493bb36bbe3e38ef5ab0
Source dataset
uspto-grants-2013_01
Patent number
US08362044B2

Reaction notes

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