Trifluoroacetic acid → 4-[[(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-[(E)-3-[[(1S)-1-(3-chlorophenyl)ethyl]amino]-3-oxo-prop-1-enyl]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a-tetradecahydrocyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxo-butanoic acid

HRID 524480Notes

Reaction equation

HRID 524480 reaction equation
[CH3:1][C:2]([CH3:57])([CH2:10][C:11]([O:13][C@H:14]1[CH2:31][CH2:30][C@@:29]2([CH3:32])[C@@H:16]([CH2:17][CH2:18][C@:19]3([CH3:54])[C@@H:28]2[CH2:27][CH2:26][C@H:25]2[C@@:20]3([CH3:53])[CH2:21][CH2:22][C@@:23]3(/[CH:39]=[CH:40]/[C:41]([NH:43][C@H:44]([C:46]4[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=4)[CH3:45])=[O:42])[CH2:35][CH2:34][C:33]([CH:36]([CH3:38])[CH3:37])=[C:24]32)[C:15]1([CH3:56])[CH3:55])=[O:12])[C:3]([O:5]C(C)(C)C)=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:52][C:48]1[CH:47]=[C:46]([C@@H:44]([NH:43][C:41](=[O:42])/[CH:40]=[CH:39]/[C@:23]23[CH2:35][CH2:34][C:33]([CH:36]([CH3:38])[CH3:37])=[C:24]2[C@@H:25]2[C@@:20]([CH3:53])([CH2:21][CH2:22]3)[C@@:19]3([CH3:54])[C@@H:28]([C@:29]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:55])([CH3:56])[C@@H:14]([O:13][C:11](=[O:12])[CH2:10][C:2]([CH3:1])([CH3:57])[C:3]([OH:5])=[O:4])[CH2:31][CH2:30]4)[CH2:27][CH2:26]2)[CH3:45])[CH:51]=[CH:50][CH:49]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 1177015001-tert-Butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((E)-3-(((S)-1-(3-chlorophenyl)ethyl)amino)-3-oxoprop-1-en-1-yl)-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-9-yl) 2,2-dimethylsuccinate

Product 1

HCID 716114564-[[(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-[(E)-3-[[(1S)-1-(3-chlorophenyl)ethyl]amino]-3-oxo-prop-1-enyl]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a-tetradecahydrocyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxo-butanoic acidYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((E)-3-(((S)-1-(3-chlorophenyl)ethyl)amino)-3-oxoprop-1-en-1-yl)-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-9-yl) 2,2-dimethylsuccinate (1556 mg, 1.934 mmol) in DCM (12 mL) stirred at room temp was added TFA (4 mL, 51.9 mmol). The reaction mixture was stirred at rt for 2 h. The mixture was evaporated to dryness, then diluted with 200 ml DCM. The organic phase was washed with saturated NaHCO3 solution (200 mL*3), water and brine. The organics were dried and concentrated under reduced pressure to afford the crude product which was purified by preparative-HPLC to give the title compound (550 mg, 38%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.40-7.17 (m, 4H), 6.85 (d, J=15.3 Hz, 1H), 5.72-5.49 (m, 2H), 5.18 (t, J=7.2 Hz, 1H), 4.50 (dd, J=5.6, 10.7 Hz, 1H), 3.28-3.10 (m, 1H), 2.74-2.62 (m, 1H), 2.62-2.50 (m, 1H), 2.24 (br. s., 3H), 2.08-1.92 (m, 2H), 1.89-0.70 (m, 49H); LC/MS: m/z calculated 747.5. Found 748.2 (M+1)+.

Workup

  1. customThe mixture was evaporated to dryness
  2. additiondiluted with 200 ml DCM
  3. washThe organic phase was washed with saturated NaHCO3 solution (200 mL*3), water and brine
  4. customThe organics were dried
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product which
  7. customwas purified by preparative-HPLC

Sources & evidence

ORD record
ord-d291a33e0e7748d0901cca21ac94d8fb
Source dataset
uspto-grants-2016_05
Patent number
US09340513B2

Reaction notes

Loading…