Ammonium Chloride → 4-[2-(5-Bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 518154ノート

反応式

HRID 518154 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([CH:8]2[S:13][CH2:12][CH2:11][CH2:10][S:9]2)[CH:7]=1.[Li+].CC([N-]C(C)C)C.[O:23]=[C:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.[NH4+].[Cl-]>C1COCC1>[C:33]([O:32][C:30]([N:27]1[CH2:28][CH2:29][C:24]([C:8]2([C:6]3[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=3[F:14])[S:9][CH2:10][CH2:11][CH2:12][S:13]2)([OH:23])[CH2:25][CH2:26]1)=[O:31])([CH3:36])([CH3:34])[CH3:35]

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2 回HCID 2724682Lithium diisopropylamideHCID 114036102-(5-Bromo-2-fluorophenyl)-1,3-dithiane

生成物 1

HCID 113064294-[2-(5-Bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester収率 40.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

A solution of 2-(5-bromo-2-fluoro-phenyl)[1,3]dithiane (19 g, 64.84 mmol) in THF (100 ml) was added to a degassed and stirred 2 M solution of LDA (32.42 ml, 64.84 mmol) in THF dry (150 ml) at −78° C. and the reaction was carried out at −20° C. for 30 min. The reaction was cooled down again to −78° C. and tert-butyl 4-oxo-1-piperidinecarboxylate (13.03 g, 65.5 mmol) in THF (100 ml) was added dropwise. After 30 min, a further portion of tert-butyl 4-oxo-1-piperidinecarboxylate was added (0.5 g, 0.25 mmol). After 1 h, the reaction mixture was poured into a saturated NH4Cl solution (200 ml) and extracted with AcOEt. The combined organic fractions were washed with water (100 ml), brine (100 ml), dried over Na2SO4, then filtered and evaporated to give a yellow oil. The crude product was purified by column chromatography (AcOEt/hexane 30/70) to give 4-[2-(5-bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester as a white solid (13 g).

後処理

  1. customa degassed
  2. customdry (150 ml) at −78° C.
  3. waitAfter 30 min
  4. waitAfter 1 h
  5. extractionextracted with AcOEt
  6. washThe combined organic fractions were washed with water (100 ml), brine (100 ml)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oil
  11. customThe crude product was purified by column chromatography (AcOEt/hexane 30/70)

出典と根拠

ORDレコード
ord-f4d508fbd56849559f54a4fd1ae3f365
出典データセット
uspto-grants-2015_08
特許番号
US09115148B2

反応ノート

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