Acetic Acid → HCID 87885175, compound

HRID 1744690Notes

Reaction equation

HRID 1744690 reaction equation
[Cl-:1].[CH:2]1([C:8]2([CH2:28][N:29]3[C:33]([CH3:35])([CH3:34])[CH2:32][O:31][C:30]3=[O:36])[CH2:13][CH2:12][N:11]([C:14]([C@@H:16]3[C@H:20]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:19][NH2+:18][CH2:17]3)=[O:15])[CH2:10][CH2:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:37][C:38]([CH3:40])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl-:1].[CH:2]1([C:8]2([CH2:28][N:29]3[C:33]([CH3:34])([CH3:35])[CH2:32][O:31][C:30]3=[O:36])[CH2:9][CH2:10][N:11]([C:14]([C@H:16]3[C@H:20]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)[CH2:19][NH+:18]([CH:38]([CH3:40])[CH3:37])[CH2:17]3)=[O:15])[CH2:12][CH2:13]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 21018571HCID 21018571, compound

Product 1

HCID 87885175HCID 87885175, compoundYield 120.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the product of step E (100 mg; 0.1916 mmol) in methylene chloride (100 mL) was converted to the free-base by washing with saturated sodium bicarbonate. The organic phase was washed with brine, dried (Na2SO4), filtered and the volatiles were removed in vacuo. The residue was dissolved in methylene chloride (2 mL) and cooled to 0° C. Acetone (111 mg; 0.14 mmol) was added, followed by acetic acid (57 mg; 0.9579 mmol) and sodium triacetoxyborohydride (0.575 mmol). The reaction mixture was stirred and allowed to warm to room temperature over 36 h at which time the reaction was quenched with saturated sodium bicarbonate. After extracting three times with methylene chloride, the organic solution was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to provide the crude residue which was purified on silica gel (93:7 methylene chloride/methanol (contaiing 10% v/v ammonium hydroxide). The product was dissolved in ethyl acetate (2 mL) and converted to the hydrochloride salt by addition of a saturated solution of hydrogen chloride in ethyl acetate (2 mL). The reaction mixture was maintained at ambient temperature for 30 min at which time the volatiles were removed in vacuo. The solid was triturated to high purity with diethyl ether which furnished 95 mg of the title compound as the hydrochloride salt [MS: m/z 528 (MH+)].

Workup

  1. washby washing with saturated sodium bicarbonate
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe volatiles were removed in vacuo
  6. dissolutionThe residue was dissolved in methylene chloride (2 mL)
  7. temperatureto warm to room temperature over 36 h at which time the reaction
  8. customwas quenched with saturated sodium bicarbonate
  9. extractionAfter extracting three times with methylene chloride
  10. washthe organic solution was washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto provide the crude residue which
  15. customwas purified on silica gel (93:7 methylene chloride/methanol (
  16. dissolutionThe product was dissolved in ethyl acetate (2 mL)
  17. additionconverted to the hydrochloride salt by addition of a saturated solution of hydrogen chloride in ethyl acetate (2 mL)
  18. temperatureThe reaction mixture was maintained at ambient temperature for 30 min at which time the volatiles
  19. customwere removed in vacuo
  20. customThe solid was triturated to high purity with diethyl ether which

Sources & evidence

ORD record
ord-313d1e9f9db94e79ba117da17f875bb4
Source dataset
uspto-grants-2006_03
Patent number
US07015235B2

Reaction notes

Loading…