Methanol → N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide

HRID 20972ノート

反応式

HRID 20972 の反応式
[Si](O[C@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)[C@@H:10]([NH:20][C:21](=[O:38])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35]OC)=[O:29])[CH:23]=1)[CH2:11]C1C=C(F)C=C(F)C=1)(C(C)(C)C)(C)C.C(OC([C@@H:65]([CH2:93][C:94]1[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=1)[C@@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:82])=[O:81])[CH2:77][N:76]1C(OC(C)(C)C)=O)[O:67][Si](C(C)(C)C)(C)C)=O)C1C=CC=CC=1.C([O:104][C:105]([N:107]1C[C@H](OCCC)C[C@@H]1[C@@H](O[Si](C(C)(C)C)(C)C)[C@@H](NC(C1C=C(C=CC=1)C(O)=O)=O)CC1C=C(F)C=C(F)C=1)=O)(C)(C)C.O=[O+][O-].[CH3:150]O>O>[OH:67][C@H:66]([C@H:75]1[CH2:79][C@@H:78]([S:80]([CH2:83][CH2:84][CH3:85])(=[O:81])=[O:82])[CH2:77][NH:76]1)[C@@H:65]([NH:107][C:105](=[O:104])[C:26]1[CH:27]=[C:22]([C:21]2[O:38][CH:11]=[CH:10][N:20]=2)[CH:23]=[C:24]([C:28]([N:30]([CH2:31][CH2:35][CH3:150])[CH2:34][CH2:33][CH3:32])=[O:29])[CH:25]=1)[CH2:93][C:94]1[CH:95]=[CH:96][CH:97]=[CH:98][CH:99]=1

参加物

7

反応物 5

HCID 887MethanolHCID 24823OzoneHCID 67315894(2r,4r)-Tert-butyl 2-((1s,2s)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylateHCID 673161403-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acidHCID 67316242(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

生成物 1

HCID 11848640N1-((1R,2S)-1-hydroxy-3-phenyl-1-((2R,4R)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide収率 64%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Step 17 (D): (2R,4R)-tert-butyl 2-((1S,2S)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylate. A solution of 130 mg (0.2 mmol) of the compound of step 17 (C) dissolved in 2 mL of methanol was treated with a solution of 240 mg (0.4 mmol) of ozone dissolved in 0.4 mL of water. After stirring at rt from 30 min, the reaction solution was partitioned between ethyl acetate and water, the organic layer was concentrated, and the crude product was purified by chromatography eluting with a gradient of 20 to 80% ethyl acetate in hexanes to provide 86 mg (64%) of the desired sulfone and 37 mg (28%) of the sulfoxide intermediate as a lower-eluting compound. 1H NMR (500 MHz, CDCl3) δ ppm 0.06 (s, 3H) 0.11 (s, 3H) 0.96 (s, 9H) 1.07 (t, J=7.32 Hz, 3H) 1.47 (s, 9H) 1.87 (dd, J=13.43, 6.71 Hz, 3H) 2.03 (s, 1H) 2.26 (t, J=12.21 Hz, 1H) 2.38 (s, 1H) 2.68 (s, 1H) 2.90 (s, 2H) 3.46 (m, 2H) 3.75 (s, 1H) 4.09 (m, 2H) 4.26 (d, J=7.02 Hz, 1H) 4.77 (m, 1H) 4.95 (m, 1H) 7.18 (m, 10H) MS (ESI) (M+H−Boc)+=575.25

後処理

  1. customthe reaction solution was partitioned between ethyl acetate and water
  2. concentrationthe organic layer was concentrated
  3. customthe crude product was purified by chromatography
  4. washeluting with a gradient of 20 to 80% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-70d510e877134b7ca2f0eeb9bf71ef49
出典データセット
uspto-grants-2010_06
特許番号
US07745470B2

反応ノート

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