2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester

HRID 1096875ノート

反応式

HRID 1096875 の反応式
[Li]CCCC.[Si:6]([O:13][CH2:14][CH2:15][O:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][N:22]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH3:23][O:24][C:25]([C:27]1[CH:28]2[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH:32]([CH2:33][C:34]=1OS(C(F)(F)F)(=O)=O)[CH2:31][N:30]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:29]2)=[O:26]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[CH3:23][O:24][C:25]([C:27]1[CH:28]2[N:43]([C:44]([O:46][C:47]([CH3:50])([CH3:48])[CH3:49])=[O:45])[CH:32]([CH2:33][C:34]=1[C:20]1[S:19][C:18]([CH2:17][O:16][CH2:15][CH2:14][O:13][Si:6]([C:9]([CH3:12])([CH3:10])[CH3:11])([CH3:7])[CH3:8])=[N:22][CH:21]=1)[CH2:31][N:30]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:29]2)=[O:26]

参加物

7

反応物 3

HCID 667839212-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazoleHCID 866370767-Trifluoromethanesulfonyloxy-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl esterHCID 178418339Butyllithium

生成物 1

HCID 866370787-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester収率 65%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

BuLi (1.6 M in hexane, 5.70 mL, 9.05 mmol) was added dropwise to a cooled (−78° C.) solution of 2-[2-(tert-butyldimethylsilanyloxy)ethoxymethyl]thiazole (1.900 g, 6.786 mmol) in THF (15 mL). The reaction mixture was stirred at −78° C. for 1 h, and ZnCl2 (1M in THF, 11.3 mL, 11.3 mmol) was added dropwise at −78° C. The cooling bath was removed, and the reaction mixture was stirred for 1 h at rt. A sol. of compound Y (2.00 g, 3.77 mmol) in THF (5 mL) was added dropwise, followed by Pd(PPh3)4 (136 mg, 0.109 mmol). The reaction mixture was stirred at rt for 2 h, partitioned between EtOAc and aq. 1M NaOH, and the layers were separated. The aq. layer was extracted with EtOAc. The combined org. extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc 7/3) yielded the title compound (1.60 g, 65%) as an orange oil. LC-MS: tR=1.19 min, ES+: 654.33.

後処理

  1. customThe cooling bath was removed
  2. stirringthe reaction mixture was stirred for 1 h at rt
  3. stirringThe reaction mixture was stirred at rt for 2 h
  4. custompartitioned between EtOAc and aq. 1M NaOH
  5. customthe layers were separated
  6. extractionThe aq. layer was extracted with EtOAc
  7. washextracts were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvents were removed under reduced pressure
  11. customPurification of the crude by FC (heptane/EtOAc 7/3)

出典と根拠

ORDレコード
ord-601339b8c34f4cb5a49071a7ddfb7057
出典データセット
uspto-grants-2012_03
特許番号
US08138340B2

反応ノート

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