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 1487484ノート

反応式

HRID 1487484 の反応式
[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]

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-36a5645a4c3a443c94096417cb15f40a
出典データセット
uspto-grants-2016_08
特許番号
US09428528B2

反応ノート

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