Ethyl Acetate → 3-(2-Methoxy-benzyl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 237298Notes

Reaction equation

HRID 237298 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12](=O)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(=O)(O)[O-].[Na+].CCOC(C)=O>CO>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 584050543-(2-Methoxy-benzoyl)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584051693-(2-Methoxy-benzyl)-azetidine-1-carboxylic acid tert-butyl esterYield 19%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(2-methoxy-benzoyl)-azetidine-1-carboxylic acid tert-butyl ester (2.1 g, 7.2 mmol) in methanol (50 mL) was added sodium borohydride (1.08 g, 28.8 mmol). After stirring for 36 h, saturated sodium bicarbonate solution and EtOAc were added. The aqueous portion was extracted three times with EtOAc and the combined organic were dried (Na2SO4) and concentrated. To a solution of this material in ethanol (50 mL) was added 10% Pd/C. This reaction was then placed on a Parr hydrogenation apparatus with 60 psi of hydrogen gas. After 72 h, the reaction mixture was filtered through a pad of Celite and the filtrate concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (370 mg, 19%). MS (ESI): mass calcd. for C16H23NO3, 277.2; m/z found, 222.2 [M-t-Bu]+. 1H NMR (CDCl3): 7.23-7.10 (m, 1H), 7.06 (d, J=7.3 Hz, 1H), 6.92-6.77 (m, 2H), 3.96 (t, J=8.0 Hz, 2H), 3.81 (s, 3H), 3.65-3.63 (m, 2H), 2.94-2.78 (m, 5H), 1.44 (s, 9H).

Workup

  1. extractionThe aqueous portion was extracted three times with EtOAc
  2. dry with materialthe combined organic were dried (Na2SO4)
  3. concentrationconcentrated
  4. additionTo a solution of this material in ethanol (50 mL) was added 10% Pd/C
  5. waitAfter 72 h
  6. filtrationthe reaction mixture was filtered through a pad of Celite
  7. concentrationthe filtrate concentrated
  8. customThe crude product was purified by RP HPLC (basic conditions)

Sources & evidence

ORD record
ord-90e86f8526d74a42be236de4b4b8f0cd
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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