Acetic Acid → Methyl 1-{[2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl]amino}cyclohexanecarboxylate

HRID 1615794ノート

反応式

HRID 1615794 の反応式
[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([CH3:11])[CH:9]=O)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:22][C:23]1([C:29]([O:31][CH3:32])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[C:1]([O:5][C:6]([NH:7][C:8]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([CH3:11])[CH2:9][NH:22][C:23]1([C:29]([O:31][CH3:32])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:20])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 176Acetic Acid2 回HCID 5003444Sodium cyanoborohydrideHCID 22645079Methyl 1-aminocyclohexane-1-carboxylate hydrochlorideHCID 86616399tert-butyl N-[2-(3,5-difluorophenyl)-1-oxopropan-2-yl]carbamate

生成物 1

HCID 66864382Methyl 1-{[2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propyl]amino}cyclohexanecarboxylate

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

A mixture of tert-butyl[1-(3,5-difluorophenyl)-1-methyl-2-oxoethyl]carbamate from Step C (500 mg, 1.75 mmol), methyl 1-aminocyclohexanecarboxylate hydrochloride from Step D (1.38 g, 8.76 mmol), and AcOH (0.301 mL, 5.26 mmol) in MeOH (15 mL) was stirred at ambient temperature for 30 min. NaCNBH3 (165 mg, 2.63 mmol) was added and the pH of the mixture was checked and adjusted to pH ˜5 as necessary by addition of AcOH. The reaction mixture was stirred at ambient temperature for 1 h, then quenched with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—100:0 to 80:20, to give the title compound. MS: m/z=427 (M+1).

後処理

  1. stirringThe reaction mixture was stirred at ambient temperature for 1 h
  2. customquenched with saturated aqueous NaHCO3 (10 mL)
  3. extractionextracted with CH2Cl2 (2×50 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography
  8. washeluting with hexane

出典と根拠

ORDレコード
ord-d94ebe2991f846b78b85ba2e75dc6236
出典データセット
uspto-grants-2014_07
特許番号
US08765759B2

反応ノート

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