Triethylamine → HCID 58573658, compound

HRID 932261Notes

Reaction equation

HRID 932261 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8](O)[C@@H:9]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([Cl:30])[CH:29]=2)[CH2:10][C@:11]([CH3:23])([CH2:20][CH:21]=[CH2:22])[C:12]([NH:14][C@@H:15]([CH2:18][CH3:19])[CH2:16][OH:17])=[O:13])=[CH:4][CH:3]=1.ClC1C=CC([C@@H](O)[C@H](C2C=NC=C(Cl)C=2)C[C@@](C)(CC=C)C(N[C@@H](CC)CO)=O)=CC=1.C(N(CC)CC)C.Cl.CN(C)C.CC1C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1>C(Cl)Cl.CC#N>[CH2:20]([C@@:11]1([CH3:23])[CH2:10][C@H:9]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([Cl:30])[CH:29]=2)[C@@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:14]([C@@H:15]([CH2:18][CH3:19])[CH2:16][OH:17])[C:12]1=[O:13])[CH:21]=[CH2:22]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 77773Toluene-p-sulphonic anhydrideHCID 10313079Trimethylamine Hydrochloride2×HCID 58573067HCID 58573067, compoundHCID 58573479HCID 58573479, compound

Product 1

HCID 58573658HCID 58573658, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The mixture of diastereomers of (S)-2-((2R,3R)-3-(4-chlorophenyl)-2-(5-chloropyridin-3-yl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide and (R)-2-((2S,3S)-3-(4-chlorophenyl)-2-(5-chloropyridin-3-yl)-3-hydroxypropyl)-N-((S)-1-hydroxybutan-2-yl)-2-methylpent-4-enamide (Example 400, Step G, 6.34 g,) was combined in DCM (68 ml) and triethylamine (13.3 ml, 95 mmol). After cooling in an ice bath, trimethylamine hydrochloride (1.953 g, 20.43 mmol) was added. 4-Methylbenzenesulfonic anhydride (17.78 g, 54.5 mmol) was added slowly as a solid, keeping the temperature below 10° C. The brownish colored solution was allowed to slowly warm to room temperature, and then stirred over night. The next day more trimethyl amine hydrochloride (0.271 mg, 2.91 mmol) was added and the solution was stirred for another day. The reaction was quenched with ice water. The layers were partitioned and the aqueous layer was washed with DCM. The combined organics were dried over MgSO4, filtered, and concentrated to provide a brown oil. The oil was dissolved in MeCN (100 ml) and then heated to 60° C. for 4 hours. The solution was concentrated and the residue dissolved in 100 ml of DCM. To this was added 100 ml of sat. NaHCO3 and the biphasic solution was stirred at rt. for 5 days. The solution was partitioned and the aqueous layer was washed with DCM. The organics were dried over MgSO4, filtered and concentrated. The product was purified by silica gel chromatography to give (3S,5R,6S)-3-allyl-6-(4-chlorophenyl)-5-(5-chloropyridin-3-yl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one as the second eluting diastereomer.

Workup

  1. temperatureAfter cooling in an ice bath
  2. customthe temperature below 10° C
  3. stirringthe solution was stirred for another day
  4. customThe reaction was quenched with ice water
  5. customThe layers were partitioned
  6. washthe aqueous layer was washed with DCM
  7. dry with materialThe combined organics were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide a brown oil
  11. temperatureheated to 60° C. for 4 hours
  12. concentrationThe solution was concentrated
  13. dissolutionthe residue dissolved in 100 ml of DCM
  14. additionTo this was added 100 ml of sat. NaHCO3
  15. stirringthe biphasic solution was stirred at rt
  16. customThe solution was partitioned
  17. washthe aqueous layer was washed with DCM
  18. dry with materialThe organics were dried over MgSO4
  19. filtrationfiltered
  20. concentrationconcentrated
  21. customThe product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d1ebac95f23447ee9ab6da9f8d6f4dff
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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