Acetic Acid → HCID 58573285, compound

HRID 932284Notes

Reaction equation

HRID 932284 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([CH2:19][CH:20]=[CH2:21])[C@@:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)([NH2:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.C(O)(=O)C.[CH3:26][C:27]([CH3:29])=O.C([BH3-])#N.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([CH2:19][CH:20]=[CH2:21])[C@@:9]([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)([NH:11][CH:27]([CH3:29])[CH3:26])[CH3:10])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5003444Sodium cyanoborohydride2×HCID 58573329HCID 58573329, compound

Product 1

HCID 58573285HCID 58573285, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of (2S,3R)-3-(3-chlorophenyl)-2-(4-chlorophenyl)hex-5-en-2-amine (Example 418, Step D) (270 mg, 0.843 mmol), acetic acid (0.243 mL, 4.22 mmol), acetone (3.10 mL, 42.2 mmol) and sodium cyanoborohydride (0.442 mL, 8.43 mmol) in methanol (4 mL) was heated to 65° C. overnight. After sixteen hours, an additional ten equivalents of sodium cyanoborohydride were added and heating continued for another five hours then equilibrated to room temperature and concentrated under reduced pressure. The concentrate was partitioned between aqueous sodium hydroxide solution and ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4 and concentrated to afford a yellow oil. The crude product was adsorbed onto silica and purified by chromatography (24 g RediSep® pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.)) eluting with 30 to 100% ethyl acetate gradient in hexane. Fractions containing product were combined and concentrated to afford the title compound as a colorless glass.

Workup

  1. waitAfter sixteen hours
  2. temperatureheating
  3. customthen equilibrated to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe concentrate was partitioned between aqueous sodium hydroxide solution and ethyl acetate
  6. extractionThe aqueous layer was extracted again with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customto afford a yellow oil
  11. custompurified by chromatography (24 g RediSep® pre-packed silica gel column (Teledyne Isco, Lincoln, Nebr.))
  12. washeluting with 30 to 100% ethyl acetate gradient in hexane
  13. additionFractions containing product
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-127f9b95eb8143f28f1113aa0556f830
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…