Hydrochloric Acid → HCID 69003659, compound

HRID 2103321Notes

Reaction equation

HRID 2103321 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=O)(C)(C)C.[F:15][C:16]([F:33])([F:32])[O:17][C:18]1[CH:31]=[CH:30][C:21]([O:22][C:23]2[CH:28]=[CH:27][C:26](O)=[CH:25][CH:24]=2)=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[ClH:67]>C1COCC1.O1CCOCC1>[ClH:67].[F:15][C:16]([F:32])([F:33])[O:17][C:18]1[CH:31]=[CH:30][C:21]([O:22][C:23]2[CH:28]=[CH:27][C:26]([O:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:25][CH:24]=2)=[CH:20][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5363146Diisopropyl azodicarboxylateHCID 212008294-[4-(Trifluoromethoxy)phenoxy]phenol

Product 1

HCID 69003659HCID 69003659, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of t-butyl-4-hydroxy-1-piperidinecarboxylate (0.40 g, 1.99 mmol) in anhydrous THF (8 mL) was added 4-(4-Trifluoromethoxy-phenoxy)-phenol (0.58 g, 2.65 mmol) and triphenylphosphine (0.63 g, 2.40 mmol). The resulting mixture was cooled to 0° C. Diisopropylazodicarboxylate (0.47 mL, 2.43 mmol) was added portionwise over a ten minute period. The reaction mixture was warmed to ambient temperature for an hour and then heated to 60° C. for 48 h. The solvent was removed in vacuo. The crude residue was purified by silica gel flash chromatography using hexane/EtOAc (gradient system) to give a yellow oil. To the oil was added 4 M HCl in dioxane (7 mL). The resulting mixture was stirred at ambient temperature 2 h. The solvent was removed under reduced pressure to obtain crude product. The residue was triturated with ether to afford the title compound (98 mg, 14%); 1H NMR (400 MHz, DMSO-d6); δ 1.85 (m, 2H), 2.10 (m, 2H), 3.06 (m, 2H), 3.23 (m, 2H), 4.61 (m, 1H), 7.02 (d, J=8.8 Hz, 2H), 7.06 (s, 3H), 7.35 (d, J=8.8 Hz, 2H), 8.92 (br s, 2H); MS (m/z) 354.4 (M+1); LC (97.5%).

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature for an hour
  2. temperatureheated to 60° C. for 48 h
  3. customThe solvent was removed in vacuo
  4. customThe crude residue was purified by silica gel flash chromatography
  5. customto give a yellow oil
  6. customThe solvent was removed under reduced pressure
  7. customto obtain crude product
  8. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-cd713043a93345d8a450f1f5c5a50bf1
Source dataset
uspto-grants-2009_08
Patent number
US07576102B2

Reaction notes

Loading…