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

HRID 514130Notes

Reaction equation

HRID 514130 reaction equation
[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]

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-7bf36e13a1094468aa1526240f432605
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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