Sodium Acetate → 5-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acid

HRID 2387176노트

반응식

HRID 2387176 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])=[C:4]([Cl:13])[CH:3]=1.[CH:14]1([C@:19]([OH:26])([CH:24]=[CH2:25])[CH2:20][C:21]([OH:23])=[O:22])[CH2:18][CH2:17][CH2:16][CH2:15]1.CC([O-])=O.[Na+].[H][H]>CC(N(C)C)=O.CCO.CC([O-])=O.CC([O-])=O.[Pd+2].[OH-].[OH-].[Pd+2]>[Cl:13][C:4]1[CH:3]=[C:2]([CH:25]=[CH:24][C:19]([CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)([OH:26])[CH2:20][C:21]([OH:23])=[O:22])[CH:7]=[CH:6][C:5]=1[C:8]([C:9]#[N:10])([CH3:12])[CH3:11]

참가 물질

9

반응물 4

HCID 517045Sodium AcetateHCID 587626012-(4-Bromo-2-chlorophenyl)-2-methylpropanenitrileHCID 58764151(3R)-3-cyclopentyl-3-hydroxypent-4-enoic acidHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 690589925-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acid수율 100%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 9942167Palladium hydroxide촉매HCID 702Ethanol용매HCID 31374Dimethylacetamide용매

실험 절차

A mixture of 2-(4-bromo-2-chloro-phenyl)-2-methyl-propionitrile (0.61 g, 2.34 mmol), from step 4 of example B(22), (3R)-3-cyclopentyl-3-hydroxypent-4-enoic acid (0.43 g, 2.34 mmol, example C(14), Pd(OAc)2 (0.01 g, 5 mol %) and NaOAc (0.24 g, 2.93 mmol). in DMAC (5 mL) was heated at 90° C. overnight. The reaction mixture was cooled to room temperature and partitioned between 1N HCl and EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated to dark brown oil. Flash column chromatography (0% to 40% EtOAc in hexanes) gave a light brown oil. The oil was dissolved in EtOH (10 mL) and treated with Pd(OH)2 (0.23 g) The mixture was stirred under a balloon of hydrogen for 1 hour. The reaction mixture was filtered through a pad of celite washing with EtOAc. The filtrate was concentrated to an orange oil and purified by flash column chromatography to give the product as a yellow solid (0.47 g, 100%). 1H NMR (300 MHz, CDCl3): δ 1.4-1.72 (m, 10 H), 1.85 (s, 6 H), 2.11-2.18 (m, 1 H), 2.56-2.73 (m, 4 H), 7.10 (d, J=7.9 Hz, 1 H), 7.26 (s, 1 H), 7.36 (d, J=7.9 Hz, 1 H). ESIMS (MNa+): 364.

후처리

  1. custompartitioned between 1N HCl and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dark brown oil
  5. customFlash column chromatography (0% to 40% EtOAc in hexanes) gave a light brown oil
  6. filtrationThe reaction mixture was filtered through a pad of celite
  7. washwashing with EtOAc
  8. concentrationThe filtrate was concentrated to an orange oil
  9. custompurified by flash column chromatography

출처 및 근거

ORD 기록
ord-6c23e24216ca43cf87b6274dbbc224f8
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268835B2

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