Hexane → (2S,3R,4S,5S,6R)-2-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

HRID 1912989노트

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HRID 1912989 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([F:17])[C:10]=2[F:18])[CH:7]=1.[Li][CH2:21]CCC.CCCCCC.C[Si](C)(C)[O:33][C@@H:34]1[C@@H:39]([O:40][Si](C)(C)C)[C@H:38]([O:45][Si](C)(C)C)[C@@H:37]([CH2:50][O:51][Si](C)(C)C)[O:36][C:35]1=[O:56]>C1(C)C=CC=CC=1.C1COCC1>[Cl:19][C:5]1[CH:4]=[CH:3][C:2]([C@@:35]2([O:56][CH3:21])[C@H:34]([OH:33])[C@@H:39]([OH:40])[C@H:38]([OH:45])[C@@H:37]([CH2:50][OH:51])[O:36]2)=[CH:7][C:6]=1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([F:17])[C:10]=1[F:18]

참가 물질

7

반응물 4

HCID 8058HexaneHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 866851071-[(5-Bromo-2-chloro-phenyl)methyl]-2,3-difluoro-4-methoxy-benzeneHCID 178418339Butyllithium

생성물 1

HCID 86685109(2S,3R,4S,5S,6R)-2-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

시약·촉매·용매 2

HCID 1140Toluene용매2회HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

1-[(5-bromo-2-chloro-phenyl)methyl]-2,3-difluoro-4-methoxy-benzene 2e (3.55 g, 10.2 mmol) was dissolved in 30 mL mixed solution (THF and toluene, v:v=1:2) and cooled to −78° C., followed by dropwise addition of a solution of nBuLi in n-hexane (4.9 mL, 12.26 mmol). After stirring for 1 hour at −78° C., a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-(trimethylsilyloxymethyl)tetrahydropyran-2-one 2f (5.24 g, 11.22 mmol, prepared according to the method in WO2010048358) in toluene (30 mL) was added. The reaction mixture was stirred for 3 hours at −78° C. Thereafter, the reaction mixture was concentrated under reduced pressure after 30 mL saturated sodium carbonate solution were added. The residue was dissolved in 30 mL saturated sodium chloride solution and extracted with ethyl acetate (50 mL×3) and the organic extract was combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system A to obtain the title compound (2S,3R,4S,5S,6R)-2-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 2g (1.31 g, white solid), yield: 27.9%. MS m/z (ESI): 429.1 [M−31]

후처리

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 3 hours at −78° C
  3. concentrationThereafter, the reaction mixture was concentrated under reduced pressure after 30 mL saturated sodium carbonate solution
  4. additionwere added
  5. dissolutionThe residue was dissolved in 30 mL saturated sodium chloride solution
  6. extractionextracted with ethyl acetate (50 mL×3)
  7. extractionthe organic extract
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe resulting residue was purified by silica gel chromatography with elution system

출처 및 근거

ORD 기록
ord-7cf755666da14294a869a9515fd9bea4
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609622B2

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