1,2-Dichloroethane → 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)acetyl)-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 513891Notes

Reaction equation

HRID 513891 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].C(Cl)CCl.[Cl:19][C:20]1[CH:66]=[CH:65][C:23]([CH2:24][N:25]([CH2:60][CH2:61][N:62]([CH3:64])[CH3:63])[CH2:26][C:27]([C@:29]23[CH2:55][C:54](=[O:56])[C:53]([CH:57]([CH3:59])[CH3:58])=[C:30]2[C@@H:31]2[C@@:44]([CH3:47])([CH2:45][CH2:46]3)[C@@:43]3([CH3:48])[C@@H:34]([C@:35]4([CH3:52])[C@@H:40]([CH2:41][CH2:42]3)[C:39]([CH3:50])([CH3:49])[C@@H:38](O)[CH2:37][CH2:36]4)[CH2:33][CH2:32]2)=[O:28])=[CH:22][CH:21]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:12][C:7]([CH3:13])([CH2:8][C:9]([O:11][C@H:38]1[CH2:37][CH2:36][C@@:35]2([CH3:52])[C@@H:40]([CH2:41][CH2:42][C@:43]3([CH3:48])[C@@H:34]2[CH2:33][CH2:32][C@H:31]2[C@@:44]3([CH3:47])[CH2:45][CH2:46][C@@:29]3([C:27](=[O:28])[CH2:26][N:25]([CH2:24][C:23]4[CH:22]=[CH:21][C:20]([Cl:19])=[CH:66][CH:65]=4)[CH2:60][CH2:61][N:62]([CH3:64])[CH3:63])[CH2:55][C:54](=[O:56])[C:53]([CH:57]([CH3:59])[CH3:58])=[C:30]32)[C:39]1([CH3:49])[CH3:50])=[O:10])[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:14]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 235551774-(Tert-butoxy)-3,3-dimethyl-4-oxobutanoic acidHCID 86690379(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)acetyl)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3a,4,5,5a,6,7,7a,8,9,10,11,11a,11b,12,13,13a-hexadecahydro-3H-cyclopenta[a]chrysen-2(5bH)-one

Product 1

HCID 866903801-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)acetyl)-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-dimethylsuccinateYield 26.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(tert-butoxy)-3,3-dimethyl-4-oxobutanoic acid (11.91 g, 58.9 mmol), N,N-dimethylpyridin-4-amine (4.50 g, 36.8 mmol) in DCM (20 mL) was added EDC (11.29 g, 58.9 mmol). The reaction mixture was stirred at rt for 1 h. Then, (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)acetyl)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-2-one (52) (5 g, 7.36 mmol) was add. Upon completion, the mixture was washed with 2 M HCl, water and brine. The organic layer was dried over Na2SO4, filtered and concentrated to give the crude product. The product was purified by a silica gel column using dichloromethane/methanol (20:1) to afford 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)acetyl)-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 (53) (1.8 g, 1.917 mmol, 26.1% yield) as an oil. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.27 (s, 4H), 4.60-4.39 (m, 1H), 3.82 (d, J=13.8 Hz, 1H), 3.59 (d, J=13.8 Hz, 1H), 3.50-3.05 (m, 3H), 2.82-2.63 (m, 2H), 2.63-0.53 (m, 67H).

Workup

  1. washUpon completion, the mixture was washed with 2 M HCl, water and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product
  6. customThe product was purified by a silica gel column

Sources & evidence

ORD record
ord-007eba5bacfd4f92b131e8ae76bee83e
Source dataset
uspto-grants-2015_08
Patent number
US09102685B2

Reaction notes

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