Hydrochloric Acid → HCID 97107398, compound

HRID 716076Notes

Reaction equation

HRID 716076 reaction equation
[BH4-].[Na+].B(F)(F)F.CC[O:9]CC.[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]=2)=[CH:22][CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].OO.Cl>C1COCC1.C(O)C.C(Cl)Cl.O>[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C@@H:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][C@H:27]2[OH:9])=[CH:22][CH:21]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 53861764HCID 53861764, compound2×

Product 1

HCID 97107398HCID 97107398, compoundYield 88.5%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium borohydride (15.5 g, 410 mmol) was dissolved in THF, and the solution was chilled to 0° C. Boron trifluoride etherate (52.3 mL, 424 mmol) was added to the solution and the mixture was allowed to warm to rt and stirred for 30 min. Then a solution of tert-butyl 4-(4-(benzyloxy)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (50 g, 137 mmol, intermediate A) in 500 mL of THF was added and the reaction mixture was stirred for 2 h at rt. A 100 mL portion of water was then added slowly to the mixture (Caution: effervescence is observed). The mixture was diluted with 100 mL of ethanol, and sodium hydroxide (228 mL, 10% solution in water, 0.684 mol) and hydrogen peroxide (20.5 mL, 0.684 mol) were added. The reaction mixture was heated to reflux temperature and stirred for 16 h. The mixture was cooled to 10° C. and diluted with 1 L of DCM. Then the pH was adjusted to 7 with 1.5 L of 1.5 N HCl. The layers were then separated, and the aqueous layer was extracted with an addition two 500 mL portions of DCM. The organic layers were combined, washed with 2×1 L of water and 200 mL of brine, dried over sodium sulfate, and evaporated in vacuo to provide an off-white solid. The solid was triturated with 500 mL of pet ether, and isolated by filtration to yield 46.5 grams of product (88%, 99.0% purity by HPLC). LC/MS RT (conditions A)=2.372 min, (M+H)+=382.0. 1H NMR (400 MHz, DMSO-d6) δ 7.47-7.42 (m, 2H), 7.42-7.36 (m, 2H), 7.36-7.28 (m, 1H), 7.14 (d, J=9.0 Hz, 2H), 6.92 (d, J=9.0 Hz, 2H), 5.07 (s, 2H), 4.74 (d, J=5.5 Hz, 1H), 4.10 (br. s., 1H), 3.94 (br. s., 1H), 3.46-3.35 (m, 1H), 2.47-2.31 (m, 2H), 1.70-1.61 (m, 1H), 1.55-1.45 (m, 2H), 1.42 (s, 9H).

Workup

  1. temperatureto warm to rt
  2. stirringthe reaction mixture was stirred for 2 h at rt
  3. additionwere added
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux temperature
  6. stirringstirred for 16 h
  7. temperatureThe mixture was cooled to 10° C.
  8. customThe layers were then separated
  9. extractionthe aqueous layer was extracted with an addition two 500 mL portions of DCM
  10. washwashed with 2×1 L of water and 200 mL of brine
  11. dry with materialdried over sodium sulfate
  12. customevaporated in vacuo
  13. customto provide an off-white solid
  14. customThe solid was triturated with 500 mL of pet ether
  15. customisolated by filtration

Sources & evidence

ORD record
ord-f6da0b74fce94033b94cc6401eb08edd
Source dataset
uspto-grants-2015_11
Patent number
US09187506B2

Reaction notes

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