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Hydrochloric Acid → Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

HRID 2061794
ノート
印刷プレビュー

反応式

HRID 2061794 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)[CH:3]=1.[Li][CH2:20]CCC.C[Si](C)(C)[O:26][C@@H:27]1[C@@H:32]([O:33][Si](C)(C)C)[C@H:31]([O:38][Si](C)(C)C)[C@@H:30]([CH2:43][O:44][Si](C)(C)C)[O:29][C:28]1=[O:49].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1(C)C=CC=CC=1.CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C@@:28]2([O:49][CH3:20])[C@H:27]([OH:26])[C@@H:32]([OH:33])[C@H:31]([OH:38])[C@@H:30]([CH2:43][OH:44])[O:29]2)=[CH:3][C:4]=1[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH3:18])=[CH:12][CH:11]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 178418339Butyllithium

生成物 1

HCID 24807437
Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 1140Toluene溶媒HCID 22635083Tetrahydrofuran toluene溶媒

反応条件

温度
-65 °C

実験手順

To a solution of Example 1B (200 g, 0.614 mol) in anhydrous toluene/THF (1.2 L, 2:1 (v/v)) was added n-BuLi (2.5 M in hexane, 295 mL) dropwise at −65° C. The reaction was stirred at −65° C. for 30 min. Then the mixture was transferred by a cannula to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one) (373 g, 0.798 mol) in toluene (1.2 L) at −65° C. The mixture was stirred at −65° C. until starting material was consumed (2 h). The reaction was quenched with hydrochloric acid (36˜38%, 113 mL, 1.35 mol) in methanol (800 mL), and stirred at room temperature overnight. The reaction was neutralized with saturated sodium bicarbonate to pH 7.5 and the organic phase was separated and the aqueous phase was extracted with ethyl acetate (2×3.0 L). The combined organic layers were washed with brine (2×2.0 L), dried over sodium sulfate and concentrated. The residue was dissolved in hot toluene (600 mL) and poured into n-hexane (2.0 L) with vigorous stirring. After stirring for 1 h, the mixture was filtered and the filter cake was dried under vacuum to give the desired product as a white solid. This solid was used without further purification in the next step. MS ESI (m/z) 439[M+1]+.

後処理

  1. customat −65° C
  2. stirringThe mixture was stirred at −65° C.
  3. customwas consumed (2 h)
  4. stirringstirred at room temperature overnight
  5. customthe organic phase was separated
  6. extractionthe aqueous phase was extracted with ethyl acetate (2×3.0 L)
  7. washThe combined organic layers were washed with brine (2×2.0 L)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in hot toluene (600 mL)
  11. additionpoured into n-hexane (2.0 L) with vigorous stirring
  12. stirringAfter stirring for 1 h
  13. filtrationthe mixture was filtered
  14. customthe filter cake was dried under vacuum

出典と根拠

ORDレコード
ord-d8e8a014ab364ba0a0b25cec3568a65f
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08283454B2

反応ノート

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