Methanesulfonic Acid → (3R,4S,5S,6R)-2-(2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

HRID 1175324ノート

反応式

HRID 1175324 の反応式
Br[C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)[C:5]([Cl:18])=[CH:4][C:3]=1[CH2:19][CH2:20][CH2:21][O:22][CH2:23][C:24]#[C:25][CH3:26].[Li][CH2:28]CCC.C[Si](C)(C)[O:34][C@@H:35]1[C@@H:40]([O:41][Si](C)(C)C)[C@H:39]([O:46][Si](C)(C)C)[C@@H:38]([CH2:51][O:52][Si](C)(C)C)[O:37][C:36]1=[O:57].CS(O)(=O)=O>C1COCC1.CCCCCC.C1(C)C=CC=CC=1.CO>[CH2:23]([O:22][CH2:21][CH2:20][CH2:19][C:3]1[CH:4]=[C:5]([Cl:18])[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH3:17])=[CH:11][CH:10]=2)=[CH:7][C:2]=1[C:36]1([O:57][CH3:28])[C@H:35]([OH:34])[C@@H:40]([OH:41])[C@H:39]([OH:46])[C@@H:38]([CH2:51][OH:52])[O:37]1)[C:24]#[C:25][CH3:26]

参加物

9

反応物 4

HCID 6395Methanesulfonic AcidHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 59557729HCID 59557729、化合物HCID 178418339Butyllithium

生成物 1

HCID 59557682(3R,4S,5S,6R)-2-(2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

実験手順

To a stirred −78° C. solution of 1-bromo-2-(3-(but-2-ynyloxy)propyl)-4-chloro-5-(4-ethoxybenzyl)benzene (BM) (0.2 g, 0.459 mmol) in 3 mL of 1:2 dry THF:toluene under Ar was added 0.22 mL of 2.5M n-BuLi in hexane (precooled to −78° C.) dropwise to insure the temperature remained below −70° C. After stirring for 40 min, the solution was transferred by cannula to a stirred −78° C. solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (0.279 g, 0.597 mmol) in 2.5 mL of toluene at a rate that maintained the reaction below −70° C. The mixture was stirred for 3 h at −78° C. prior to addition of MeSO3H (0.093 g, 0.964 mmol) in 2.5 mL of methanol below −75° C. After complete addition, the reaction solution was gradually warmed to room temperature and stirred overnight. After quenching by saturated aq. NaHCO3, the aqueous layer was extracted twice with EtOAc. The combined organic portions were washed with brine and dried over Na2SO4. After concentration, the residue was purified by preparative TLC (eluting with EtOAc:PE=1:5) to obtain 0.11 g of intermediate BN.

後処理

  1. customremained below −70° C
  2. customwas transferred by cannula to a stirred −78° C.
  3. temperaturemaintained
  4. customthe reaction below −70° C
  5. stirringThe mixture was stirred for 3 h at −78° C.
  6. additionAfter complete addition
  7. stirringstirred overnight
  8. customAfter quenching by saturated aq. NaHCO3
  9. extractionthe aqueous layer was extracted twice with EtOAc
  10. washThe combined organic portions were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationAfter concentration
  13. customthe residue was purified by preparative TLC (eluting with EtOAc:PE=1:5)

出典と根拠

ORDレコード
ord-4823d03c13d84fc2b5cef61386c274de
出典データセット
uspto-grants-2010_11
特許番号
US07838498B2

反応ノート

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