Tris(1,1-dimethylethyl)phosphine → tert-Butyl 3-(7-amino-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

HRID 424589ノート

反応式

HRID 424589 の反応式
C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:15]1[CH:16]=[CH:17][C:18]2[N:23]([CH:24]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25]3)[CH2:22][CH2:21][S:20][C:19]=2[CH:36]=1.[Li+].C[Si]([N-:42][Si](C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:42][C:15]1[CH:16]=[CH:17][C:18]2[N:23]([CH:24]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25]3)[CH2:22][CH2:21][S:20][C:19]=2[CH:36]=1

参加物

7

反応物 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 59144137tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

生成物 1

HCID 59144157tert-Butyl 3-(7-amino-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate収率 83%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
100 °C

実験手順

Tris(dibenzylideneacetone)dipalladium(0) (0.056 g, 0.062 mmol) in THF (3 mL) was treated with tri-tert-butylphosphine 10% wt in hexanes (0.748 mL, 0.247 mmol) and was stirred vigorously under argon atmosphere for 10 minutes. tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate (0.49 g, 1.233 mmol) in THF (9 mL) and IM LiHMDS in THF (3.70 mL, 3.70 mmol) were added to the mixture. The reaction was sealed, placed in a preheated oil bath, and refluxed at 100° C. The solution was cooled to room temperature, treated with 1M TBAF in THF (8 mL), and was stirred for 40 minutes. The mixture was concentrated and treated with 1N NaOH (50 mL). The mixture was transferred to a separatory funnel, diluted with water (50 mL), and extracted with EtOAc (2×50 mL). The organic phase was washed with brine (50 mL) and dried (Na2SO4). The crude material was subject to flash chromatography on silica gel (25-70% EtOAc/hexanes). The collected fractions were concentrated to give a clear brown oil (0.34 g, 83%). 1H NMR (CDCl3) δ 6.64 (d, J=8.7 Hz, 1H), 6.48 (s, 1H), 6.39 (brs, 1H), 4.08-4.02 (m, 1H), 3.70-3.07 (m, 6H), 3.09-3.07 (m, 2H), 2.08-1.92 (m, 2H), 1.46 (s, 9H); ESI-MS (m/z, %): 338, 336 (MH+, 40), 282, 280 (100).

後処理

  1. customThe reaction was sealed
  2. customplaced in a preheated oil bath
  3. temperatureThe solution was cooled to room temperature
  4. stirringwas stirred for 40 minutes
  5. concentrationThe mixture was concentrated
  6. additiontreated with 1N NaOH (50 mL)
  7. customThe mixture was transferred to a separatory funnel
  8. additiondiluted with water (50 mL)
  9. extractionextracted with EtOAc (2×50 mL)
  10. washThe organic phase was washed with brine (50 mL)
  11. dry with materialdried (Na2SO4)
  12. concentrationThe collected fractions were concentrated

出典と根拠

ORDレコード
ord-6142b130aec54f5689dfd68c75972887
出典データセット
uspto-grants-2012_01
特許番号
US08106043B2

反応ノート

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