Potassium hydroxy sulfite → (s)-2-((s)-3-Acetamido-3-((r)-sec-butyl)-2-oxopyrrolidin-1-yl)-n-((1r,2s)-1-hydroxy-3-phenyl-1-((2r,4r)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132969Notes

Reaction equation

HRID 132969 reaction equation
C(OC([C@@H:11]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:12]([C@H:21]1[CH2:25][C@@H:24]([S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH2:23][N:22]1C(OC(C)(C)C)=O)[O:13][Si](C(C)(C)C)(C)C)=O)C1C=CC=CC=1.[C:46]([NH:49][C@:50]1([C@@H:105]([CH2:107][CH3:108])[CH3:106])[CH2:54][CH2:53][N:52]([C@@H:55]([CH2:96][CH2:97][C:98]2[CH:103]=[CH:102][CH:101]=[CH:100][CH:99]=2)[C:56]([NH:58][C@@H](CC2C=C(F)C=C(F)C=2)[C@@H]([C@H]2C[C@H](OC3C=CC=CN=3)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)O)=[O:57])[C:51]1=[O:104])(=[O:48])[CH3:47].OOS([O-])=O.[K+]>CO.O>[C:46]([NH:49][C@:50]1([C@@H:105]([CH2:107][CH3:108])[CH3:106])[CH2:54][CH2:53][N:52]([C@@H:55]([CH2:96][CH2:97][C:98]2[CH:103]=[CH:102][CH:101]=[CH:100][CH:99]=2)[C:56]([NH:58][C@@H:11]([CH2:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C@H:12]([OH:13])[C@H:21]2[CH2:25][C@@H:24]([S:26]([CH2:29][CH2:30][CH3:31])(=[O:27])=[O:28])[CH2:23][NH:22]2)=[O:57])[C:51]1=[O:104])(=[O:48])[CH3:47]

Participants

6

Reactant 3

HCID 23707502Potassium hydroxy sulfiteHCID 67315894(2r,4r)-Tert-butyl 2-((1s,2s)-2-(benzyloxycarbonyl)-1-(tert-butyldimethylsilyloxy)-3-phenylpropyl)-4-(propylsulfonyl)pyrrolidine-1-carboxylateHCID 69195135(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamide

Product 1

HCID 69195114(s)-2-((s)-3-Acetamido-3-((r)-sec-butyl)-2-oxopyrrolidin-1-yl)-n-((1r,2s)-1-hydroxy-3-phenyl-1-((2r,4r)-4-(propylsulfonyl)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamideYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Step 22 (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 22 (C) dissolved in 2 mL of methanol was treated with a solution of 240 mg (0.4 mmol) of oxone dissolved in 0.4 mL of water. After stirring at rt for 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 0.06 (s, 3 H) 0.11 (s, 3 H) 0.96 (s, 9 H) 1.07 (t, J=7.32 Hz, 3 H) 1.47 (s, 9 H) 1.87 (dd, J=13.43, 6.71 Hz, 3 H) 2.03 (s, 1 H) 2.26 (t, J=12.21 Hz, 1 H) 2.38 (s, 1 H) 2.68 (s, 1 H) 2.90 (s, 2 H) 3.46 (m, 2 H) 3.75 (s, 1 H) 4.09 (m, 2 H) 4.26 (d, J=7.02 Hz, 1 H) 4.77 (m, 1 H) 4.95 (m, 1 H) 7.18 (m, 10 H) 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-48a25d8ac98442d39b7b27a25d5cbcf1
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

Loading…