Hydrochloric Acid → 3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-5-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)oxazolidin-2-one

HRID 513900Notes

Reaction equation

HRID 513900 reaction equation
C([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:48])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:47])[CH2:12][CH2:13][C@@:14]3([CH:31]4[O:35][C:34](=[O:36])[N:33]([C:37]5([C:40]6[N:45]=[CH:44][C:43]([Cl:46])=[CH:42][N:41]=6)[CH2:39][CH2:38]5)[CH2:32]4)[CH2:26][C:25](=[O:27])[C:24]([CH:28]([CH3:30])[CH3:29])=[C:15]32)[C:6]1([CH3:50])[CH3:49])(=O)C.Cl>O1CCOCC1.CO>[Cl:46][C:43]1[CH:42]=[N:41][C:40]([C:37]2([N:33]3[CH2:32][CH:31]([C@:14]45[CH2:26][C:25](=[O:27])[C:24]([CH:28]([CH3:29])[CH3:30])=[C:15]4[C@@H:16]4[C@@:11]([CH3:47])([CH2:12][CH2:13]5)[C@@:10]5([CH3:48])[C@@H:19]([C@:20]6([CH3:23])[C@@H:7]([CH2:8][CH2:9]5)[C:6]([CH3:49])([CH3:50])[C@@H:5]([OH:4])[CH2:22][CH2:21]6)[CH2:18][CH2:17]4)[O:35][C:34]3=[O:36])[CH2:39][CH2:38]2)=[N:45][CH:44]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86690396(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate

Product 1

HCID 866903953-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-5-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)oxazolidin-2-oneYield 17.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-2-oxooxazolidin-5-yl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate (107) (350 mg, 0.496 mmol) in 1,4-dioxane (10 mL) and methanol (5 mL) was added hydrochloric acid (5 mL, 165 mmol). The reaction mixture was stirred at 40° C. overnight. The solvents were removed under reduced pressure and taken up in DCM (100 ml), washed with sat. NaHCO3 (20 ml), water (20 ml) and brine (20 ml), dried over sodium sulfate, filtered and concentrated to give residue, which was subjected to a silica gel column eluting with petroleum ether/EtOAc (6:1 to 3:1) to give 3-(1-(5-chloropyrimidin-2-yl)cyclopropyl)-5-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)oxazolidin-2-one (130 mg, 0.087 mmol, 17%) as a white solid. LC/MS: m/z calculated 663.4. found 664.3 (M+1)+.

Workup

  1. customThe solvents were removed under reduced pressure
  2. washwashed with sat. NaHCO3 (20 ml), water (20 ml) and brine (20 ml)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give residue, which
  7. washeluting with petroleum ether/EtOAc (6:1 to 3:1)

Sources & evidence

ORD record
ord-549cdc6aade848eaa900d344afd29e60
Source dataset
uspto-grants-2015_08
Patent number
US09102685B2

Reaction notes

Loading…