Hydrochloric Acid → (RS)-1-(6-Hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol Hydrochloride

HRID 278417Notes

Reaction equation

HRID 278417 reaction equation
C[O:2][C:3]1[CH:27]=[CH:26][C:6]2[CH2:7][CH:8]([CH2:10][N:11]3[CH2:16][CH2:15][C:14]([CH2:18][C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=4)([OH:17])[CH2:13][CH2:12]3)[O:9][C:5]=2[CH:4]=1.B(Br)(Br)Br.C(Cl)[Cl:33].C([O-])(O)=O.[Na+].Cl.Cl.OC1C=CC2CC(CN3CCC(C(C)C4C=CC=CC=4)(O)CC3)OC=2C=1>C(Cl)Cl.CO>[ClH:33].[OH:2][C:3]1[CH:27]=[CH:26][C:6]2[CH2:7][CH:8]([CH2:10][N:11]3[CH2:12][CH2:13][C:14]([CH2:18][C:19]4[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=4)([OH:17])[CH2:15][CH2:16]3)[O:9][C:5]=2[CH:4]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 22277759Boron tribromide dichloromethaneHCID 22628365HCID 22628365, compoundHCID 70046464(RS)-1-(6-hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(methyl-benzyl)-piperidin-4-ol hydrochloride

Product 1

HCID 22628393(RS)-1-(6-Hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol Hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-8 °C

Procedure

(RS)-1-(6-methoxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (1.24g, 3.37 mmol) dissolved in 35 ml of CH2Cl2 was cooled to −8° C. and 1M BBr3—CH2Cl2 solution (6.8 ml, 2 eq.) was added dropwise under argon. The violet suspension was allowed to warm to room temperature and then stirred for 30 minutes. The reaction was then cooled to 0° C. and MeOH (9 ml) was added to quench the reaction, followed by satd. NaHCO3 (50 ml). The organic phase was separated and the aqueous phase was extracted with CH2Cl2 (2×50 ml). The combined organic extracts were dried with Na2SO4 then filtered and evaporated. The resulting yellow foam was chromatographed over SiO2 (Merck 230-400 mesh) eluting with MeOH—CH2Cl2 (1:19) followed by MeOH—CH2Cl2 (1:9) to provide a yellow foam which was dissolved in MeOH (5 ml) and treated with 1N HCl (3.4 ml) to provide (RS)-1-(6-hydroxy-2,3-dihydro-benzofuran-2-ylmethyl)-4-(methyl-benzyl)-piperidin-4-ol hydrochloride (0.92g, 70%) as a white solid and mixture of E/Z isomers. Mp. 203-205° C. MS: m/e=354.3(M+H+)

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction was then cooled to 0° C.
  3. customto quench
  4. customthe reaction
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with CH2Cl2 (2×50 ml)
  7. dry with materialThe combined organic extracts were dried with Na2SO4
  8. filtrationthen filtered
  9. customevaporated
  10. customThe resulting yellow foam was chromatographed over SiO2 (Merck 230-400 mesh)
  11. washeluting with MeOH—CH2Cl2 (1:19)
  12. customto provide a yellow foam which
  13. customto provide

Sources & evidence

ORD record
ord-f8021079a71f4cbbb000ce9ed19e43f4
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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