1,2-Dichloroethane → 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-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) 2,2-dimethylsuccinate

HRID 513901Notes

Reaction equation

HRID 513901 reaction equation
[C:1]([O:5][C:6](=[O:14])[C:7]([CH3:13])([CH3:12])[CH2:8][C:9]([OH:11])=[O:10])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:17]=[N:18][C:19]([C:22]2([N:25]3[CH2:29][CH:28]([C@:30]45[CH2:56][C:55](=[O:57])[C:54]([CH:58]([CH3:60])[CH3:59])=[C:31]4[C@@H:32]4[C@@:45]([CH3:48])([CH2:46][CH2:47]5)[C@@:44]5([CH3:49])[C@@H:35]([C@:36]6([CH3:53])[C@@H:41]([CH2:42][CH2:43]5)[C:40]([CH3:51])([CH3:50])[C@@H:39]([OH:52])[CH2:38][CH2:37]6)[CH2:34][CH2:33]4)[O:27][C:26]3=[O:61])[CH2:24][CH2:23]2)=[N:20][CH:21]=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:12][C:7]([CH3:13])([CH2:8][C:9]([O:11][C@H:39]1[CH2:38][CH2:37][C@@:36]2([CH3:53])[C@@H:41]([CH2:42][CH2:43][C@:44]3([CH3:49])[C@@H:35]2[CH2:34][CH2:33][C@H:32]2[C@@:45]3([CH3:48])[CH2:46][CH2:47][C@@:30]3([C@@H:28]4[O:27][C:26](=[O:61])[N:25]([C:22]5([C:19]6[N:18]=[CH:17][C:16]([Cl:15])=[CH:21][N:20]=6)[CH2:23][CH2:24]5)[CH2:29]4)[CH2:56][C:55](=[O:57])[C:54]([CH:58]([CH3:60])[CH3:59])=[C:31]32)[C:40]1([CH3:51])[CH3:50])=[O:10])[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:14].[CH3:12][C:7]([CH3:13])([CH2:8][C:9]([O:52][C@H:39]1[CH2:38][CH2:37][C@@:36]2([CH3:53])[C@@H:41]([CH2:42][CH2:43][C@:44]3([CH3:49])[C@@H:35]2[CH2:34][CH2:33][C@H:32]2[C@@:45]3([CH3:48])[CH2:46][CH2:47][C@@:30]3([C@H:28]4[O:27][C:26](=[O:61])[N:25]([C:22]5([C:19]6[N:20]=[CH:21][C:16]([Cl:15])=[CH:17][N:18]=6)[CH2:24][CH2:23]5)[CH2:29]4)[CH2:56][C:55](=[O:57])[C:54]([CH:58]([CH3:59])[CH3:60])=[C:31]32)[C:40]1([CH3:50])[CH3:51])=[O:10])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:14]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 235551774-(Tert-butoxy)-3,3-dimethyl-4-oxobutanoic acidHCID 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-one

Product 2

HCID 866903971-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-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) 2,2-dimethylsuccinateHCID 866903981-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-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) 2,2-dimethylsuccinate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-tert-butoxy-3,3-dimethyl-4-oxobutanoic acid 10 (119 mg, 0.587 mmol), 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 (108) (130 mg, 0.196 mmol), EDC (188 mg, 0.978 mmol) and DMAP (71.7 mg, 0.587 mmol) in DCM (5 mL) was stirred at rt overnight. After the reaction finished, the mixture was diluted with DCM (25 ml), washed with water (2×15 ml) and brine (20 ml), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography using petroleum ether/EtOAc (6:1 to 3:1) as eluent to give the two diastereomeric products 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((S)-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) 2,2-dimethylsuccinate (109) and 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-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) 2,2-dimethylsuccinate (110) in the amounts of (80 mg, 45%) and (50 mg, 22%) as white solids. The stereochemical assignments for each diastereomer were not made. Compound A (tentatively designated as 109): LC/MS: m/z calculated 847.5. found 848.3 (M+1)+. Compound B (tentatively designated as 110): LC/MS: m/z calculated 847.5. found 848 (M+1)+.

Workup

  1. washwashed with water (2×15 ml) and brine (20 ml)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7e54c3ffce39419f9233c802bfd9d029
Source dataset
uspto-grants-2015_08
Patent number
US09102685B2

Reaction notes

Loading…