Sodium Carbonate → (+/-)-Tert-butyl 1-[3-({[4-(acetoxymethyl)phenyl](cyclopentyl)acetyl}-amino)benzyl]cyclopropanecarboxylate

HRID 1475653ノート

反応式

HRID 1475653 の反応式
[C:1]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13]([OH:15])=O)=[CH:8][CH:7]=1)(=[O:3])[CH3:2].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:41][C:42]1[CH:43]=[C:44]([CH:56]=[CH:57][CH:58]=1)[CH2:45][C:46]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[C:1]([O:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([CH:12]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13]([NH:41][C:42]2[CH:43]=[C:44]([CH:56]=[CH:57][CH:58]=2)[CH2:45][C:46]2([C:49]([O:51][C:52]([CH3:55])([CH3:53])[CH3:54])=[O:50])[CH2:48][CH2:47]2)=[O:15])=[CH:10][CH:11]=1)(=[O:3])[CH3:2]

参加物

8

反応物 6

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136423[4-(Acetoxymethyl)phenyl](cyclopentyl)acetic acidHCID 58136514tert-Butyl 1-(3-aminobenzyl)cyclopropanecarboxylate

生成物 1

HCID 68170303(+/-)-Tert-butyl 1-[3-({[4-(acetoxymethyl)phenyl](cyclopentyl)acetyl}-amino)benzyl]cyclopropanecarboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

9.50 g (34.4 mmol) of (+/−)-[4-(acetoxymethyl)phenyl](cyclopentyl)acetic acid were dissolved in 67.5 ml of DMF, and 5.58 g (41.25 mmol) of 1-hydroxy-1H-benzotriazole hydrate (HOBt) were added. The mixture was cooled to 0° C., and 15.0 ml (85.95 mmol) of N,N-diisopropylethylamine and 10.63 g (42.97 mmol) of tert-butyl 1-(3-aminobenzyl)cyclopropanecarboxylate, dissolved in a little DMF, were added. 14.38 g (37.82 mmol) of HATU were then added in several portions, and the reaction mixture was slowly warmed to RT and then stirred overnight. The mixture was then added to saturated aqueous sodium carbonate solution. After phase separation, the aqueous phase was extracted repeatedly with ethyl acetate, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase dichloromethane/ethyl acetate 50:1→20:1). This gave 12.86 g of the target compound (69.4% of theory).

後処理

  1. additionwere added
  2. temperaturethe reaction mixture was slowly warmed to RT
  3. customAfter phase separation
  4. extractionthe aqueous phase was extracted repeatedly with ethyl acetate
  5. washthe combined organic phases were washed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography on silica gel (mobile phase dichloromethane/ethyl acetate 50:1→20:1)

出典と根拠

ORDレコード
ord-c5058435428945b6bd62037aedc20f94
出典データセット
uspto-grants-2015_04
特許番号
US09018258B2

反応ノート

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