Acetic Acid → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-4-((dimethylamino)methyl)-3-methylnaphthalen-2-yl)acetic acid

HRID 514130Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 514130
[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH:23]=O)[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O.[CH3:50][NH:51][CH3:52].CO>O.CN(C=O)C.C(Cl)Cl.CCO>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH2:23][N:51]([CH3:52])[CH3:50])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Komponenten

10

Edukt 5

HCID 176Acetic Acid2×HCID 674Dimethylamine2×HCID 887Methanol2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86691564Ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-4-formyl-3-methylnaphthalen-2-yl)acetate

Produkt 1

HCID 671261972-Tert-butoxy-2-(1-(4-chlorophenyl)-4-((dimethylamino)methyl)-3-methylnaphthalen-2-yl)acetic acidAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A suspension of ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-4-formyl-3-methylnaphthalen-2-yl)acetate (6.0 mg, 13.9 μmol), EtOH (absolute, 500 μL), NaBH(OAc)3 (8.8 mg, 41.7 μmol), and glacial AcOH (4 μL, 70 μmol) was treated with a solution of N,N-dimethylamine in MeOH (2 M, 35 μL, 69.5 μmol). DCM (50 μL) was added to improve solubility. The reaction was sealed and heated to 70° C. Conversion was limited, so more N,N-dimethylamine in MeOH (2 M, 170 μL, 0.337 mmol), glacial AcOH (20 μL, 0.35 mmol), NaBH(OAc)3 (50 mg, 0.236 mmol), and DMF (500 μL) were added. Heating was continued. Once conversion was achieved, LiOH monohydrate (200 mg, 4.7 mmol) and H2O (1.0 mL) were added. The reaction was sealed and heated to 100° C. overnight. Afterward, the reaction was filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (mono trifluoroacetic acid salt) (1.0 mg, 13%). LCMS-ESI+ (m/z): [M+H]+ calcd for C26H31ClNO3: 440.2; Found: 440.0.

Aufarbeitung

  1. customThe reaction was sealed
  2. temperatureHeating
  3. customThe reaction was sealed
  4. temperatureheated to 100° C. overnight
  5. filtrationAfterward, the reaction was filtered through a 0.45 micron
  6. filtrationfilter
  7. customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-7bf36e13a1094468aa1526240f432605
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102614B2

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