Hydrochloric Acid → HCID 69001498, compound

HRID 2103318Notes

Reaction equation

HRID 2103318 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=O)(C)(C)C.[CH:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:18]=[C:17]([O:25][C:26]2[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=2)[CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[ClH:66]>C1COCC1.O1CCOCC1>[ClH:66].[F:22][C:21]([F:23])([F:24])[C:20]1[CH:15]=[CH:16][C:17]([O:25][C:26]2[CH:31]=[CH:30][C:29]([O:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:28][CH:27]=2)=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 170230p-(4-(Trifluoromethyl)phenoxy)phenolHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 69001498HCID 69001498, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of t-butyl-4-hydroxy-1-piperidine carboxylate (1.0 g, 5.0 mmol) in anhydrous THF (5 mL) was added 4-[(4-trifluoromethyl)phenoxy]phenol (1.65 g, 6.5 mmol) in THF (5 mL) and triphenyl phosphine (1.57 g, 6 mmol) in THF (5mL). The resulting mixture was cooled to 0° C. using ice-water bath and purged with nitrogen. Diisopropyl azodicarboxylate (1.21 g, 6 mmol) was dissolved in 5 mL of THF and added to above solution drop wise over a period of 30 min under nitrogen. Reaction then was stirred at 0° C. for 0.5 h heated at 70° C. for 16 h. THF was removed in vacuo and crude mixture was purified by silica gel flash chromatography (10% EtOAc/Hexane) to obtain the product. To a solution of the product in dioxane (4 mL) was added 4M HCl in dioxane (10 mL) at rt and the resulting mixture was stirred for 2 h at that temperature. The solvent was removed in vacuo and residue was triturated with ether to obtain a white solid (1.21 g, 65%): MS; m/z 338.4 (M+H), 1H NMR (400 MHz, DMSO-d6); δ 1.83-1.90 (m, 2H), 2.09-2.14 (m, 2H), 3.03-3.09 (m, 2H), 3.20-3.26 (m, 2H), 3.32 (s, 1H), 4.62-4.66 (m, 1H), 7.06-7.10 (m, 7H), 7.70 (d, 2H, J=8.8 Hz), 9.08 (s, 2H); HPLC (UV); 97%.

Workup

  1. custompurged with nitrogen
  2. additionadded to above solution drop wise over a period of 30 min under nitrogen
  3. customReaction
  4. temperatureheated at 70° C. for 16 h
  5. customTHF was removed in vacuo and crude mixture
  6. customwas purified by silica gel flash chromatography (10% EtOAc/Hexane)
  7. customto obtain the product
  8. stirringthe resulting mixture was stirred for 2 h at that temperature
  9. customThe solvent was removed in vacuo and residue
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-0f4340f7660d44b1a6ad2fb2510930fd
Source dataset
uspto-grants-2009_08
Patent number
US07576102B2

Reaction notes

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