Sodium hydride → Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-{[9-(tert-butyldimethyl-silanyloxy)nonyl]methylamino}bicyclo[2.2.1]hept-2-ylester

HRID 1670897ノート

反応式

HRID 1670897 の反応式
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH3:29])[C@H:21]1[C@H:25]2[CH2:26][CH2:27][C@@H:22]1[C@H:23]([OH:28])[CH2:24]2)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].C([O:32][C:33](=O)[C:34]([OH:45])([C:40]1[S:41][CH:42]=[CH:43][CH:44]=1)[C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)C.[Cl-].[NH4+]>C1(C)C=CC=CC=1.CCOCC>[C:6]([Si:3]([CH3:4])([CH3:5])[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH3:29])[C@H:21]1[C@H:25]2[CH2:26][CH2:27][C@@H:22]1[C@H:23]([O:28][C:33](=[O:32])[C:34]([OH:45])([C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)[C:40]1[S:41][CH:42]=[CH:43][CH:44]=1)[CH2:24]2)([CH3:9])([CH3:8])[CH3:7]

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 12723738Ethyl 2-hydroxy-2,2-DI(thiophen-2-YL)acetateHCID 67348477(1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol

生成物 1

HCID 67349685Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-{[9-(tert-butyldimethyl-silanyloxy)nonyl]methylamino}bicyclo[2.2.1]hept-2-ylester

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
80 °C

実験手順

Sodium hydride (254 mg, 60% suspension in mineral oil, 6.35 mmol) was added to a solution of (1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol (1.01 g, 2.54 mmol) in dry toluene (20 mL) at 0° C. under a nitrogen atmosphere. As soon as the gas evolution subsided hydroxy-di-thiophen-2-yl-acetic acid ethyl ester (817 mg, 3.04 mmol) was added in portions, and when the gas evolution stopped the reaction mixture was heated at 80° C. on a preheated sand bath. After 2.5 h the reaction mixture was poured onto satd ammonium chloride (aq) and ether. The layers were separated, the aqueous layer extracted with ether, and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated to dryness to afford a light brown viscous oil. The crude product was purified by column chromatography over silica gel using a gradient of 1-40% ethyl acetate in DCM as eluent to afford the product as a very light brown viscous oil.

後処理

  1. additionwas added in portions, and when the gas evolution
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with ether
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customto afford a light brown viscous oil
  9. customThe crude product was purified by column chromatography over silica gel using a gradient of 1-40% ethyl acetate in DCM as eluent
  10. customto afford the product as a very light brown viscous oil

出典と根拠

ORDレコード
ord-acca2f39cf5f47158b0a72edc402f1ff
出典データセット
uspto-grants-2011_08
特許番号
US07994211B2

反応ノート

読み込み中…