Water → 4-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 72617

반응식

HRID 72617 반응식
[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15]([CH2:18][C:19]3[CH:24]=[C:23]([C@H:25]4[C@H:30]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[C@@H:29]([O:39][CH2:40][C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C@H:28]([O:47][CH2:48][C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)[C@@H:27]([CH2:55][O:56][CH2:57][C:58]5[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=5)[O:26]4)[CH:22]=[CH:21][C:20]=3Br)[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:65]1(B(O)O)[CH2:67][CH2:66]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15]([CH2:18][C:19]3[CH:24]=[C:23]([C@H:25]4[C@H:30]([O:31][CH2:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[C@@H:29]([O:39][CH2:40][C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C@H:28]([O:47][CH2:48][C:49]5[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=5)[C@@H:27]([CH2:55][O:56][CH2:57][C:58]5[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=5)[O:26]4)[CH:22]=[CH:21][C:20]=3[CH:65]3[CH2:67][CH2:66]3)[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 529135254-benzyl-6-[2-bromo-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine

생성물 1

HCID 529135264-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine수율 95%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 22272177Toluene water용매

반응 조건

온도
100 °C

실험 절차

To a stirred solution of 4-benzyl-6-[2-bromo-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine (0.35 g, 0.38 mmol) in toluene:water (10:1 mixture, 10 mL) was added cyclopropylboronic acid (49.2 mg, 0.5731 mmol) tricyclohexylphosphine (26.7 mg, 0.0955 mmol), and potassium phosphate (0.28 g, 1.34 mmol). The reaction mixture was degassed for 45 min then palladium (II) acetate (8.5 mg, 0.03821 mmol) was added. After heating overnight at 100° C., the reaction mixture was cooled to room temperature and water (20 mL) was added. The resulting mixture was extracted with ethyl acetate (2×25 mL), washed with water and brine, then dried over sodium sulfate, concentrated and purified by column chromatography to furnish 4-benzyl-6-[2-cyclopropyl-5-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-benzyl]-3,4-dihydro-2H-benzo[1,4]oxazine (317 mg). The product was taken up for the next step without characterization.

후처리

  1. customThe reaction mixture was degassed for 45 min
  2. temperaturethe reaction mixture was cooled to room temperature
  3. extractionThe resulting mixture was extracted with ethyl acetate (2×25 mL)
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by column chromatography

출처 및 근거

ORD 기록
ord-6678cb7f5c784103b1b4fdd366803d9e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828951B2

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