Dichloromethane → (5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester

HRID 1487558ノート

反応式

HRID 1487558 の反応式
[F:1][CH:2]([F:29])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4].[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:43]=[CH:42][C:41](Cl)=[CH:40][N:39]=1)([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C(O)(C)C.O>[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:43]=[CH:42][C:41]([C:15]2[CH:16]=[CH:17][C:12]([C@H:8]3[O:7][C:6]([CH3:27])([CH3:28])[N:5]([C:3](=[O:4])[CH:2]([F:29])[F:1])[C@@H:9]3[CH2:10][F:11])=[CH:13][CH:14]=2)=[CH:40][N:39]=1)([CH3:33])([CH3:31])[CH3:32]

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 72710400tert-Butyl ((5-chloropyrimidin-2-yl)methyl)carbamateHCID 866954142,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone

生成物 1

HCID 86695517(5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester収率 36.4%

試薬・触媒・溶媒 1

HCID 21889133Propan-2-ol--water (1/1)溶媒

反応条件

温度
140 °C

実験手順

To a stirred solution of 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-3-yl}-ethanone (0.286 g, 0.694 mmol) and (5-Chloro-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester (0.2 g, 0.694 mmol) in isopropylalcohol:water (2:1, 6 mL) is added K2CO3 (0.287 g, 2.083 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 20 minutes followed by addition of Pd(dppf)Cl2.CH2Cl2 (0.028 g, 0.035 mmol). The resulting reaction mixture is heated to 140° C. for 20 minutes in a microwave. Solvent is evaporated in vacuo and the crude material is diluted using water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by column chromatography using Combi-flash eluting with 75% ethyl acetate in hexane to afford the title compound (0.125 g): 1H NMR (400 MHz, DMSO-d6) δ: 1.40 (s, 9H), 1.52 (s, 3H), 1.60 (s, 3H), 4.36 (d, J=6.16 Hz, 2H), 4.54-4.58 (m, 0.5H), 4.66-4.73 (m, 1H), 4.82-4.85 (m, 0.5H), 4.91-4.95 (m, 1H), 5.28 (d, J=3.52 Hz, 1H), 6.64 (t, J=52.44 Hz, 1H), 7.32 (t, J=6.04 Hz, 1H), 7.62 (d, J=8.04 Hz, 2H), 7.86 (d, J=8.04 Hz, 2H), 9.10 (s, 2H). LC-MS (m/z): [M+H]=495.

後処理

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 20 minutes
  4. additionfollowed by addition of Pd(dppf)Cl2
  5. customThe resulting reaction mixture
  6. customSolvent is evaporated in vacuo
  7. additionthe crude material is diluted
  8. extractionextracted with ethyl acetate
  9. dry with materialOrganic layer is dried over sodium sulphate
  10. concentrationconcentrated
  11. custompurified by column chromatography
  12. washeluting with 75% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-e3cdaef3579a439c9b6c67b2c4d80603
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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