Triethylamine → HCID 86690403, compound

HRID 513905Notes

Reaction equation

HRID 513905 reaction equation
[CH3:1][C:2]([CH3:52])([CH2:6][C:7]([O:9][C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@@H:12]([CH2:13][CH2:14][C@:15]3([CH3:49])[C@@H:24]2[CH2:23][CH2:22][C@H:21]2[C@@:16]3([CH3:48])[CH2:17][CH2:18][C@@:19]3([C@@H:36]([OH:47])[CH2:37][NH:38][CH2:39][C:40]4[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=4)[CH2:31][C:30](=[O:32])[C:29]([CH:33]([CH3:35])[CH3:34])=[C:20]32)[C:11]1([CH3:51])[CH3:50])=[O:8])[C:3]([O-:5])=[O:4].[Na+].S([O-])(O)=O.[CH3:58][C:59]([CH3:63])(N)[CH:60]=O.[CH3:64][CH2:65][N:66]([CH2:69]C)[CH2:67]C.[BH3-]C#N.[Na+]>CO>[CH3:52][C:2]([CH3:1])([CH2:6][C:7]([O:9][C@H:10]1[CH2:27][CH2:26][C@@:25]2([CH3:28])[C@@H:12]([CH2:13][CH2:14][C@:15]3([CH3:49])[C@@H:24]2[CH2:23][CH2:22][C@H:21]2[C@@:16]3([CH3:48])[CH2:17][CH2:18][C@@:19]3([C@@H:36]([OH:47])[CH2:37][N:38]([CH2:39][C:40]4[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=4)[CH2:64][CH2:65][N:66]([CH3:69])[CH3:67])[CH2:31][C:30](=[O:32])[C:29]([CH:33]([CH3:35])[CH3:34])=[C:20]32)[C:11]1([CH3:50])[CH3:51])=[O:8])[C:3]([O:5][C:59]([CH3:63])([CH3:60])[CH3:58])=[O:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 86690404HCID 86690404, compoundHCID 86690405HCID 86690405, compound

Product 1

HCID 86690403HCID 86690403, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
35 °C

Procedure

Added a solution of 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-2-((4-chlorobenzyl)amino)-1-hydroxyethyl)-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 (55 g, 69.3 mmol) dissolved in methanol (825 mL), dimethyl amino acetaldehyde hydrogen sulfite sodium salt (66.8 g, 0.35 mol) and Et3N (38.7 g, 0.38 mol) into a reactor. The reaction was stirred for 2-3 hrs at 30-40° C. under nitrogen protection. NaBH3CN (8.8 g, 0.14 mol) was added and stirred at 30-40° C. under nitrogen protection for 13-15 hrs. Next, the reaction temperature was adjusted to 50-60° C. and stirred for 3-5 hrs. The reaction mixture was then concentrated to 275 mL and then DCM (550 mL) was added, followed by water (440 mL). The two phases were separated and the water phase was extracted with DCM (twice with 385 mLs each time). The organic phase was washed with water (twice with 358 mLs each time). Next, the organic phase was concentrated to give 1-tert-butyl 4-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-((R)-2-((4-chlorobenzyl)(2-(dimethylamino)ethyl)amino)-1-hydroxyethyl)-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 43 g oil. Yield is 71%. 1HNMR (400 MHz, CDCl3) δ=7.27-7.29 (m, 4H), 4.46-4.50 (m, 1H), 4.08-4.13 (m, 2H), 4.00-4.02 (m, 1H), 3.59-3.60 (m, 1H), 3.09 (m, 1H), 2.03-2.67 (m, 14H), 0.62-1.42 (m, 57H);

Workup

  1. stirringstirred at 30-40° C. under nitrogen protection for 13-15 hrs
  2. customwas adjusted to 50-60° C.
  3. stirringstirred for 3-5 hrs
  4. concentrationThe reaction mixture was then concentrated to 275 mL
  5. additionDCM (550 mL) was added
  6. customThe two phases were separated
  7. extractionthe water phase was extracted with DCM (twice with 385 mLs each time)
  8. washThe organic phase was washed with water (twice with 358 mLs each time)
  9. concentrationNext, the organic phase was concentrated

Sources & evidence

ORD record
ord-25ef79475d6341f79889f2981563609b
Source dataset
uspto-grants-2015_08
Patent number
US09102685B2

Reaction notes

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