Hydrochloric Acid → HCID 46735689, compound

HRID 2103313Notes

Reaction equation

HRID 2103313 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=O)(C)(C)C.[O:15]([C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=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:62]>C1COCC1.O1CCOCC1>[ClH:62].[O:15]([C:22]1[CH:23]=[CH:24][C:25]([O:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:26][CH:27]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 132544-PhenoxyphenolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 46735689HCID 46735689, compoundYield 68%

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-phenoxyphenol (1.21 g, 6.5 mmol) in THF (5 mL) and triphenyl phosphine (1.57 g, 6 mmol) in THF (5 mL). 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 period of 20 min under nitrogen. Reaction then was heated at rt for 3 h and 70° C. for 48 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 3 h at that temperature. The solvent was removed in vacuo and residue was triturated with ether to obtain a white crystalline solid (918 mg, 68%): MS; m/z 270.5 (M+H); 1H NMR (400 MHz, DMSO-d6); δ 1.81-1.87 (m, 2H), 2.07-2.12 (m, 2H), 3.02-3.08 (m, 2H), 3.19-3.25 (m, 2H), 3.56 (s, 1H), 4.57-4.61 (m, 1H), 6.92-7.10 (m, 7H), 7.33-7.37 (m, 2H), 8.91 (s, 2H); HPLC (UV); 96%. Elemental analysis. Calc C 66.77 H 6.59 N 4.58. Found C 65.82 H 6.70 N 4.77.

Workup

  1. custompurged with nitrogen
  2. additionadded to above solution drop wise over period of 20 min under nitrogen
  3. customReaction
  4. temperaturethen was heated at rt for 3 h and 70° C. for 48 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. customThe solvent was removed in vacuo and residue
  9. customwas triturated with ether

Sources & evidence

ORD record
ord-fcc61fc9aa5b4d38b0b80b09c5aa481b
Source dataset
uspto-grants-2009_08
Patent number
US07576102B2

Reaction notes

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