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

HRID 1615831노트

반응식

HRID 1615831 반응식
[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]

참가 물질

6

반응물 4

HCID 176Acetic Acid2회HCID 5003444Sodium cyanoborohydrideHCID 22645079Methyl 1-aminocyclohexane-1-carboxylate hydrochlorideHCID 86616399tert-butyl N-[2-(3,5-difluorophenyl)-1-oxopropan-2-yl]carbamate

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a9c59f331c5747fab0c2d93f234485c6
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765759B2

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