Tert-butyl 3-(2-methyl-4-(pyrrolidin-1-ylmethyl)phenoxy)azetidine-1-carboxylate → 1-(4-(Azetidin-3-yloxy)-3-methylbenzyl)pyrrolidine

HRID 1035182Notes

Reaction equation

HRID 1035182 reaction equation
[CH3:1][C:2]1[CH:19]=[C:18]([CH2:20][N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:17]=[CH:16][C:3]=1[O:4][CH:5]1[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1>Cl.CO>[NH:7]1[CH2:6][CH:5]([O:4][C:3]2[CH:16]=[CH:17][C:18]([CH2:20][N:21]3[CH2:22][CH2:23][CH2:24][CH2:25]3)=[CH:19][C:2]=2[CH3:1])[CH2:8]1

Participants

4

Reactant 1

HCID 58043113Tert-butyl 3-(2-methyl-4-(pyrrolidin-1-ylmethyl)phenoxy)azetidine-1-carboxylate

Product 1

HCID 666561701-(4-(Azetidin-3-yloxy)-3-methylbenzyl)pyrrolidineYield 81.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

Intermediate 19A (0.75 g, 2.15 mmol) was dissolved in a 4.0 M solution of HCl in MeOH (20 mL) and the reaction mixture was stirred at RT over night. The mixture was concentrated and the residue was dissolved in water. The solution was basified to pH=10 with aqueous NaOH (1.0 M) and extracted with DCM (4×30 mL). The combined organic phases were filtered through a phase separator and the solvent was removed by evaporation. There was obtained 0.43 g (72%) of 19B as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 1.71-1.83 (m, 4H), 2.33 (s, 3H), 2.43-2.55 (m, 4H), 3.52 (s, 2H), 3.73-3.85 (m, 2H), 3.85-3.96 (m, 2H), 4.91-5.03 (m, 1H), 6.52 (d, 1H), 6.57 (s, 1H), 7.17 (d, 1H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in water
  3. extractionextracted with DCM (4×30 mL)
  4. filtrationThe combined organic phases were filtered through a phase separator
  5. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-76f50e58552740e98f576a391ad70310
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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