Hydrochloric Acid → 2-(2,4-Difluorophenyl)-6-(1-hydroxy-1-methylethyl)isonicotinic acid

HRID 1909125노트

반응식

HRID 1909125 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([CH3:21])=[CH2:20])[N:18]=1)[C:12]([O:14]C)=[O:13].[BH4-].C([N+](CC)(CC)CC)C.[OH-:32].[Na+].Cl>CO.COCCOC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([OH:32])([CH3:21])[CH3:20])[N:18]=1)[C:12]([OH:14])=[O:13]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 28251Tetraethylammonium tetrahydroborate2회HCID 67339607Methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinate

생성물 1

HCID 673396622-(2,4-Difluorophenyl)-6-(1-hydroxy-1-methylethyl)isonicotinic acid수율 74.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 80711,2-Dimethoxyethane용매

실험 절차

To a solution of methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinate (0.29 g, 1.01 mmol) in methanol (5.1 mL) and DME (5.1 mL) was added cobalt(II)mesotetraphenylporphine (6.8 mg, 10.1 mmol). The mixture was stirred at ambient temperature. After 18 h, tetraethylammonium borohydride (73.5 mg, 0.51 mmol) was added. After 15 min, additional tetraethylammonium borohydride (0.14 g, 1.01 mmol) was added. After 1.5 h, sodium hydroxide (1.0 M in water; 2.03 mL, 2.03 mmol) was added. The mixture was heated to 50° C. After 1 h, HCl (0.17 mL, 2.03 mmol) was added and the mixture was concentrated. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (0.22 g). MS 294.1 (M+1).

후처리

  1. waitAfter 15 min
  2. waitAfter 1.5 h
  3. temperatureThe mixture was heated to 50° C
  4. waitAfter 1 h
  5. concentrationthe mixture was concentrated
  6. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-a420fb67075e4d03a90704c842265576
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598209B2

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