Water → (1-(4-(Azetidin-3-yloxy)-2-methylbenzyl)-4-methylpiperidin-4-yl)methanol

HRID 1035236Notes

Reaction equation

HRID 1035236 reaction equation
[OH:1][CH2:2][C:3]1([CH3:29])[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:27]=[CH:26][C:13]([O:14][CH:15]3[CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16]3)=[CH:12][C:11]=2[CH3:28])[CH2:5][CH2:4]1.C(O)(C(F)(F)F)=O.O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[NH:17]1[CH2:18][CH:15]([O:14][C:13]2[CH:26]=[CH:27][C:10]([CH2:9][N:6]3[CH2:7][CH2:8][C:3]([CH2:2][OH:1])([CH3:29])[CH2:4][CH2:5]3)=[C:11]([CH3:28])[CH:12]=2)[CH2:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 58043112HCID 58043112, compound

Product 1

HCID 66656363(1-(4-(Azetidin-3-yloxy)-2-methylbenzyl)-4-methylpiperidin-4-yl)methanolYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 69B (3.10 g, 7.66 mmol) in DCM (100 mL) was added TFA (30 mL) and the reaction mixture was stirred at RT for 2 h. The mixture was transferred to a reparatory funnel and water was added. The aqueous phase was carefully basified with Na2CO3. The organic layer was separated and the basic aqueous layer was extracted ten times with. The combined organic layers were filtered through a phase separator and the solvent was removed by evaporation. The residue was dissolved in a mixture of THF (30 mL) and an aqueous solution of NaOH (1M, 40 mL). The mixture was stirred at RT for 4 h and then the solution was concentrated using a rotavapor. The aqueous residue was extracted several times with DCM. The aqueous layer was diluted with a saturated solution of NaHCO3 and the mixture was further extracted with DCM. The combined organic layers were filtered through a phase separator and the solvent was removed by evaporation. There was obtained 1.65 g (71%) of 69C as an oil. 1H NMR (500 MHz, CDCl3): δ 0.95 (s, 3H), 1.32 (m, 2H), 1.54 (m, 2H), 2.32 (m, 2H), 2.54 (m, 2H), 3.38 (s, 2H), 3.42 (s, 2H), 3.83 (m, 2H), 3.95 (m, 2H), 4.97 (m, 1H), 6.50 (dd, 1H), 6.57 (s, 1H), 7.16 (d, 1H), MS (APCI+) m/z 305 [M+H]+.

Workup

  1. customThe mixture was transferred to a reparatory funnel
  2. customThe organic layer was separated
  3. extractionthe basic aqueous layer was extracted ten times with
  4. filtrationThe combined organic layers were filtered through a phase separator
  5. customthe solvent was removed by evaporation
  6. dissolutionThe residue was dissolved in a mixture of THF (30 mL)
  7. stirringThe mixture was stirred at RT for 4 h
  8. concentrationthe solution was concentrated
  9. extractionThe aqueous residue was extracted several times with DCM
  10. additionThe aqueous layer was diluted with a saturated solution of NaHCO3
  11. extractionthe mixture was further extracted with DCM
  12. filtrationThe combined organic layers were filtered through a phase separator
  13. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-4cd9a20613a44c5aa3f79a84f6e5a5e8
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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