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 20972Notes

Reaction equation

HRID 20972 reaction equation
[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

Participants

7

Reactant 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

Product 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-dipropylisophthalamideYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-70d510e877134b7ca2f0eeb9bf71ef49
Source dataset
uspto-grants-2010_06
Patent number
US07745470B2

Reaction notes

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