Oxygen → (4S,5S)-3,4,5-tris-benzyloxy-2-{4-fluoro-3-[4-(oxetan-3-yloxy)-benzyl]-phenyl}-6,6-bis-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-2-ol

HRID 659901노트

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HRID 659901 반응식
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=O.Br[C:9]1[CH:10]=[CH:11][C:12]([F:27])=[C:13]([CH:26]=1)[CH2:14][C:15]1[CH:25]=[CH:24][C:18]([O:19][CH:20]2[CH2:23][O:22][CH2:21]2)=[CH:17][CH:16]=1.CON(C)[C:31](=[O:83])[C@H:32]([O:75]CC1C=CC=CC=1)[C@@H:33]([O:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C@H:34]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:35]([OH:58])([CH2:47][O:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=1)[CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=1.[Al].O1C[CH2:89][CH2:88][CH2:87]1>C(OCC)C>[CH2:1]([O:75][CH:32]1[C@@H:33]([O:67][CH2:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[C@H:34]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:35]([CH2:47][O:48][CH2:49][C:50]2[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=2)([CH2:36][O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[O:58][C:31]1([C:9]1[CH:10]=[CH:11][C:12]([F:27])=[C:13]([CH2:14][C:15]2[CH:25]=[CH:24][C:18]([O:19][CH:20]3[CH2:23][O:22][CH2:21]3)=[CH:17][CH:16]=2)[CH:26]=1)[OH:83])[C:2]1[CH:89]=[CH:88][CH:87]=[CH:4][CH:3]=1

참가 물질

8

반응물 6

HCID 977OxygenHCID 8028Tetrahydrofuran2회HCID 5359268AluminumHCID 59226798(2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amideHCID 666159473-[4-(5-Bromo-2-fluoro-benzyl)-phenoxy]-oxetaneHCID 178418339Butyllithium

생성물 1

HCID 86639771(4S,5S)-3,4,5-tris-benzyloxy-2-{4-fluoro-3-[4-(oxetan-3-yloxy)-benzyl]-phenyl}-6,6-bis-(4-methoxy-benzyloxymethyl)-tetrahydro-pyran-2-ol수율 59%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

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온도
10 °C

실험 절차

n-Butyl lithium (1.12 mL, 2.5 M/hexanes, 3.0 equivalents) was added dropwise (1 drop every 5 seconds) to an oxygen degassed solution of 3-[4-(5-Bromo-2-fluoro-benzyl)-phenoxy]-oxetane (942.0 mg, 2.79 mmol) in anhydrous tetrahydrofuran (3.0 mL) at −78° C. and the resulting solution was stirred at this temperature for 1 hour. A solution of (2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amide I-1g (725.0 mg, 0.930 mmol) in anhydrous tetrahydrofuran (1.5 mL) was then added dropwise very slowly (0.9 ml/hour) and the resulting mixture was stirred at −78° C. for an additional hour before warming to 10° C. over 12 hours (put in a deep Dewar covered with aluminum foil to maintain cold temperature). The reaction was diluted with diethyl ether and quenched by the dropwise addition of aqueous 1N hydrochloric acid solution. The resulting biphasic mixture was stirred at room temperature for 15 minutes. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (eluting with a gradient of 10 to 40% ethyl acetate in heptane) to afford the product as a mixture of isomers (535 mg, 59% yield).

후처리

  1. stirringthe resulting mixture was stirred at −78° C. for an additional hour
  2. temperatureto maintain cold temperature)
  3. customquenched by the dropwise addition of aqueous 1N hydrochloric acid solution
  4. stirringThe resulting biphasic mixture was stirred at room temperature for 15 minutes
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude residue was purified by flash chromatography over silica gel (
  11. washeluting with a gradient of 10 to 40% ethyl acetate in heptane)
  12. customto afford the product
  13. additionas a mixture of isomers (535 mg, 59% yield)

출처 및 근거

ORD 기록
ord-e4edcd28f2ba4fe79b79690e7a3ddb8f
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08080580B2

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