Ethyl Acetate → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-formyl-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

HRID 1482116Notes

Reaction equation

HRID 1482116 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]=C)[C:38]2=[N:44][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:50][CH2:49][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[C:28]([F:46])[C:29]=2[C:30]2[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].I([O-])(=O)(=O)=[O:53].[Na+].CC(=O)OCC>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([CH:42]=[O:53])[C:38]2=[N:44][C:35]3=[CH:36][N:37]2[C:12]=1[N:13]1[CH2:50][CH2:49][C:16]([CH3:51])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:48])[O:23][C:24]2[CH:25]=[CH:26][C:27]([F:47])=[C:28]([F:46])[C:29]=2[C:30]2[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 23667635Sodium periodateHCID 118316351Methyl(2S)-2-(tert-butoxy)-2-[(22S)-5-ethenyl-16,17-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

Product 1

HCID 118316352Methyl(2S)-2-(tert-butoxy)-2-[(22S)-16,17-difluoro-5-formyl-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetateYield 93%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl(2S)-2-(tert-butoxy)-2-[(22S)-5-ethenyl-16,17-difluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (0.15 g, 0.214 mmol, 1.0 equiv) was dissolved in dioxane (6.41 mL) and water (2.14 mL). To this solution was added sodium periodate (0.16 g, 0.748 mmol, 3.5 equiv) and 4% osmium tetroxide (0.136 g, 0.021 mmol, 0.1 equiv). The mixture was stirred at r.t. for 2 hours. Then it was diluted by EA, washed by water, dried over MgSO4, concentrated to load onto 12 g ISCO column and purified with 0-100% EtOAc[2% TEA]/Hexane to afford the product (0.14 g, 93%). 1H NMR (400 MHz, CDCl3) δ 11.23 (s, 1H), 8.28 (d, J=7.8 Hz, 1H), 8.07 (s, 1H), 7.92 (s, 1H), 7.58 (t, J=7.8 Hz, 1H), 7.39 (d, J=1.5 Hz, 1H), 7.10 (d, J=9.3 Hz, 1H), 6.72-6.65 (m, 1H), 6.19-5.95 (m, 1H), 4.53-4.43 (m, 1H), 4.05-3.93 (m, 1H), 3.80-3.74 (m, 1H), 3.71 (s, 3H), 3.50 (d, J=16.1 Hz, 2H), 3.21-3.13 (m, 1H), 2.77 (s, 3H), 2.74-2.66 (m, 1H), 1.96 (d, J=13.6 Hz, 2H), 1.86-1.69 (m, 8H), 1.29 (s, 3H), 1.25 (s, 9H), 1.13 (d, J=6.0 Hz, 3H); LCMS (ESI, M+1): 704.25.

Workup

  1. washwashed by water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. custompurified with 0-100% EtOAc[2% TEA]/Hexane

Sources & evidence

ORD record
ord-00e68f4a4c944fa9915018da7fa8b24a
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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