Cesium carbonate → (4S,5R)-4-Fluoromethyl-5-{4-[6-(isopropyl amino-methyl)-pyridin-3-yl]-phenyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1520483노트

반응식

HRID 1520483 반응식
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:32]([O-])([O-])=O.[Cs+].[Cs+].Br[C:39]1[CH:40]=[CH:41][C:42]([CH2:45][NH:46]C(C)C)=[N:43][CH:44]=1.[CH2:50]([CH2:53]OC)OC.O>O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:16]=[CH:17][C:18]([C:39]3[CH:44]=[N:43][C:42]([CH:45]([CH:50]([CH3:53])[CH3:32])[NH2:46])=[CH:41][CH:40]=3)=[CH:19][CH:20]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 18180031Water 1,2-dimethoxyethaneHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylateHCID 62959892[(5-Bromopyridin-2-yl)methyl](propan-2-yl)amine

생성물 1

HCID 86695440(4S,5R)-4-Fluoromethyl-5-{4-[6-(isopropyl amino-methyl)-pyridin-3-yl]-phenyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

To a solution of (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (270 mg, 0.620 mmol) in dimethoxyethane:water (8:2, 3.6 mL) is added Cs2CO3 (504 mg, 1.55 mmol) and (5-Bromo-pyridin-2-ylmethyl)-isopropyl-amine (156 mg, 0.682 mmol) at room temperature. Reaction mixture is degassed with nitrogen for 30 minutes then Pd(PPh3)4 (71 mg, 0.062 mmol) is added. The resulting reaction mixture is heated to 90° C. for 4 hours. The reaction mixture is diluted with water and ethyl acetate. The organic layer is separated, dried over sodium sulphate and solvent is evaporated in vacuo. The crude is purified by column chromatography eluting in 5% methanol in CH2Cl2 to afford the title compound (100 mg). LC-MS (m/z): [M+H]=458.2.

후처리

  1. customReaction mixture
  2. customis degassed with nitrogen for 30 minutes
  3. customThe resulting reaction mixture
  4. customThe organic layer is separated
  5. dry with materialdried over sodium sulphate and solvent
  6. customis evaporated in vacuo
  7. customThe crude is purified by column chromatography
  8. washeluting in 5% methanol in CH2Cl2

출처 및 근거

ORD 기록
ord-cc45d32db553484db31f009d9ab1a0a2
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073894B2

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