Oxalyl chloride → HCID 67777052, compound

HRID 2405476Notes

Reaction equation

HRID 2405476 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH3:42])([CH3:41])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:40])([C@@:17]4([CH3:39])[C@H:22]([CH2:23][CH2:24]2)[C@H:21]2[C@H:30]([C:33]([CH3:35])=[CH2:34])[CH2:31][CH2:32][C@:20]2([C:36](O)=[O:37])[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].C(Cl)(=O)C(Cl)=O.[C:49]([O:53][C:54](=[O:61])[N:55]([CH2:57][CH2:58][CH2:59][NH2:60])[CH3:56])([CH3:52])([CH3:51])[CH3:50]>ClCCCl.O>[C:49]([O:53][C:54]([N:55]([CH3:56])[CH2:57][CH2:58][CH2:59][NH:60][C:36]([C@:20]12[CH2:32][CH2:31][C@@H:30]([C:33]([CH3:35])=[CH2:34])[C@@H:21]1[C@@H:22]1[C@@:17]([CH3:39])([CH2:18][CH2:19]2)[C@@:16]2([CH3:40])[C@@H:25]([C@:26]3([CH3:29])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:42])([CH3:41])[C:11]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][CH:9]=2)=[CH:28][CH2:27]3)[CH2:24][CH2:23]1)=[O:37])=[O:61])([CH3:52])([CH3:50])[CH3:51]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 2756543tert-butyl N-(3-aminopropyl)-N-methylcarbamateHCID 54759950(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-9-(4-methoxycarbonylphenyl)-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysene-3a-carboxylic acid

Product 1

HCID 67777052HCID 67777052, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a flask containing (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylic acid (0.1 g, 0.175 mmol) was added oxalyl chloride (2M in DCM) (3 mL, 6.00 mmol). The mixture bubbled vigorously for several minutes, then bubbling ceased and the clear solution was stirred at rt for 3 h. The mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane and concentrated two additional times. The crude product was diluted with DCE (2 mL) and Hunig'sBase (0.152 mL, 0.873 mmol) and N-(3-aminopropyl)-N-methylcarbamic acid tert-butyl ester (0.061 g, 0.324 mmol) were added to the mixture. After stirring the mixture for 19 h at rt, the mixture was diluted with 10 mL of water and was extracted with dichloromethane (3×10 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by Biotage flash chromatography using a 0-5% MeOH in DCM gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(tert-butoxycarbonyl(methyl)amino)propylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (122 mg, 0.164 mmol, 94% yield) as a white foam. LCMS: m/e 741.6 (M−H)−, 3.41 min (method 3). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.90 (d, J=8.24 Hz, 2H), 7.17 (d, J=8.24 Hz, 2H), 6.89 (br. s., 1H), 5.26 (d, J=4.58 Hz, 1H), 4.74 (d, J=1.83 Hz, 1H), 4.57 (s, 1H), 3.88 (s, 3H), 3.40-3.04 (m, 5H), 2.81 (s, 3H), 2.51 (t, J=10.83 Hz, 1H), 2.19-2.04 (m, 2H), 1.99-1.87 (m, 1H), 1.68 (s, 3H), 1.45 (s, 9H), 0.98 (s, 3H), 1.52-0.95 (m, 20H), 0.97 (s, 3H), 0.94 (s, 3H), 0.90 (s, 6H).

Workup

  1. customThe mixture bubbled vigorously for several minutes
  2. custombubbling
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. concentrationconcentrated two additional times
  6. additionwere added to the mixture
  7. stirringAfter stirring the mixture for 19 h at rt
  8. extractionwas extracted with dichloromethane (3×10 mL)
  9. dry with materialThe combined organic layers were dried with Na2SO4
  10. customThe drying agent was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by Biotage flash chromatography
  13. additionThe fractions containing the expected product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d8dce1c1f35f4041b367b6e5a95e544b
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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