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

HRID 514130ノート

反応式

HRID 514130 の反応式
[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]

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
70 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-7bf36e13a1094468aa1526240f432605
出典データセット
uspto-grants-2015_08
特許番号
US09102614B2

反応ノート

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