Cesium carbonate → (4S,5R)-5-[4-(6-Cyano-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1487514ノート

反応式

HRID 1487514 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([O-])([O-])=O.[Cs+].[Cs+].Br[C:39]1[CH:40]=[CH:41][C:42]([C:45]#[N:46])=[N:43][CH:44]=1>C(COC)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]([C:45]#[N:46])=[CH:41][CH:40]=3)=[CH:19][CH:20]=2)[O:10][C:9]1([CH3:30])[CH3:31])=[O:7])([CH3:3])([CH3:4])[CH3:2]

参加物

8

反応物 3

HCID 10796Cesium carbonateHCID 8171545-Bromopyridine-2-carbonitrileHCID 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-carboxylate

生成物 1

HCID 86695461(4S,5R)-5-[4-(6-Cyano-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester収率 42.4%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 18180031Water 1,2-dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

To stirred 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 (0.75 g, 1.72 mmol) in dimethoxyethane:water (8:2, 10 mL) is added Cs2CO3 (1.12 g, 3.44 mmol) and 5-Bromo-pyridine-2-carbonitrile (0.347 g, 1.89 mmol). Reaction mixture is degassed with nitrogen for 30 minutes, followed by addition of Pd(PPh3)4 (0.199 g, 0.172 mmol). The resulting reaction mixture heated to 90° C. for 3 hours. Diluted with water (20 mL) and ethyl acetate (40 mL). The organic layer is separated, dried over sodium sulphate and solvent is evaporated in vacuo to get crude material purified by column chromatography eluting in 15% ethyl acetate in hexane to afford title compound (0.3 g). 1H-NMR (400 MHz, DMSO-d6): δ: 1.43 (s, 9H), 1.51 (s, 3H), 1.63 (s, 3H), 3.83-3.90 (m, 1H), 4.47-4.58 (m, 2H), 4.75-4.93 (m, 2H), 5.15 (d, 1H, J=7.2 Hz), 7.64 (d, 2H, J=8.28 Hz), 7.87 (d, 2H, J=8.24 Hz), 8.15 (d, 1H, J=8.16 Hz), 8.36 (dd, 1H, J=8.2 Hz, J=2.2 Hz), 9.12 (d, 1H, J=2.24 Hz), LC-MS (m/z): [M+H]=412.1.

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. customto get crude material
  8. custompurified by column chromatography
  9. washeluting in 15% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-6949048d96cf46f298f994553f39cb39
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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