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Sodium Bicarbonate → Methyl 3-{[(2R*,6R*)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoate

HRID 2208670
ノート
印刷プレビュー

反応式

HRID 2208670 の反応式
[NH2:1][C:2]1[C:3]([CH3:16])=[C:4]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH2:17]([N:24]1[C@@H:29]([CH3:30])[CH2:28][C:27](=O)[CH2:26][C@H:25]1[CH3:32])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C1COCC1.C(O)(C(F)(F)F)=O>[CH2:17]([N:24]1[C@H:29]([CH3:30])[CH2:28][CH:27]([NH:1][C:2]2[C:3]([CH3:16])=[C:4]([CH:9]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH2:26][C@H:25]1[CH3:32])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59342390(2R,6S)-1-benzyl-2,6-dimethylpiperidin-4-oneHCID 68295733Methyl 3-amino-2-methyl-5-(trifluoromethyl)benzoate

生成物 1

HCID 86719532Methyl 3-{[(2R*,6R*)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoate収率 37%

試薬・触媒・溶媒 2

HCID 6422Trifluoroacetic acid溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a stirred solution of methyl 3-amino-2-methyl-5-(trifluoromethyl)benzoate (400 mg, 1.72 mmol) in THF (15 mL) and TFA (491 uL) was added (2R,6S)-1-benzyl-2,6-dimethylpiperidin-4-one (410 mg, 1.89 mmol) at 0° C. The mixture was stirred at 60° C. for 1 hour under nitrogen atmosphere. Then the mixture was cooled to 0° C. in an ice bath, sodium triacetoxyborohydride (765 mg, 3.43 mmol) was added. The reaction mixture was stirred at 23° C. for 2 hours. Then aq. NaHCO3 was added at 0° C. until pH8-9, and the content was extracted with ethylacetate. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=3/1) to give the titled compound as a colorless oil. (278 mg, 37% yield). 1H-NMR (400M Hz, CDCl3) δppm; 7.21-7.40 (m, 6H), 6.90 (s, 1H), 3.95 (d, J=14.0 Hz, 1H), 3.90 (s, 3H), 3.60-3.73 (m, 2H), 3.46 (d, J=14.0 Hz, 1H), 3.08-3.12 (m, 1H), 2.98-3.03 (m, 1H), 2.30 (s, 3H), 2.02-2.08 (m, 1H), 1.83-1.88 (m, 1H), 1.52-1.60 (m, 1H), 1.17-1.26 (m, 1H), 1.11 (d, J=6.8 Hz, 3H), 1.13 (d, J=6.4 Hz, 3H).

後処理

  1. temperatureThen the mixture was cooled to 0° C. in an ice bath
  2. stirringThe reaction mixture was stirred at 23° C. for 2 hours
  3. extractionthe content was extracted with ethylacetate
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=3/1)

出典と根拠

ORDレコード
ord-3f04278d7b5b4e02b5bbd136b2b9db37
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09376422B2

反応ノート

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