3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 1-Azetidinecarboxylic acid, 3-[(3S)-3-fluoro-1-pyrrolidinyl]-, 1,1-dimethylethyl ester

HRID 1945554Notes

Reaction equation

HRID 1945554 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:14][C@H:15]1[CH2:19][CH2:18][NH:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:17]2[CH2:18][CH2:19][C@H:15]([F:14])[CH2:16]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 16217739(s)-3-Fluoropyrrolidine hydrochloride

Product 1

HCID 596055011-Azetidinecarboxylic acid, 3-[(3S)-3-fluoro-1-pyrrolidinyl]-, 1,1-dimethylethyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A 25 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (0.4 g, 2.34 mmol), (S)-3-fluoropyrrolidine hydrochloride (0.35 g, 2.8 mmol) and 4 Å molecular sieves (2.43 g) in DCE (10 mL). The reaction mixture was stirred for 2.5 h at room temperature. Sodium triacetoxyborohydride (0.99 g, 4.68 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, EtOAc: cyclohexane, gradient 30:70 to 100:0) to give 3-((S)-3-Fluoropyrrolidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a colourless oil (0.342 g, 60%). 1H NMR (300 MHz, CDCl3): δ 5.34-5.10 (m, 1 H), 4.01-3.93 (m, 2 H), 3.91-3.81 (m, 2 H), 3.41-3.31 (m, 1 H), 2.94-2.67 (m, 3 H), 2.56-2.46 (m, 1 H), 2.24-2.06 (m, 2 H), 1.43 (s, 9 H).

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, EtOAc: cyclohexane, gradient 30:70 to 100:0)

Sources & evidence

ORD record
ord-7f905b2663e84098bc87822402171034
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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