Acetic Acid → Methyl 1-((6-(tert-butyldimethylsilyloxy)naphthalen-2-yl)methyl)azetidine-3-carboxylate

HRID 2404146Notes

Reaction equation

[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH:19]=O)[CH:13]=[CH:12]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC(O)=O.[NH:25]1[CH2:28][CH:27]([C:29]([O:31][CH3:32])=[O:30])[CH2:26]1.[BH3-]C#N.[Na+]>ClCCCl>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][N:25]1[CH2:28][CH:27]([C:29]([O:31][CH3:32])=[O:30])[CH2:26]1)[CH:13]=[CH:12]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 85 °C

Procedure

6-(tert-butyldimethylsilyloxy)-2-naphthaldehyde (4.0 g, 14 mmol), AcOH (1.8 g, 28 mmol) and methyl azetidine-3-carboxylate (3.2 g, 28 mmol, 2.0 equiv) in DCE (30 mL) were stirred at 85° C. for 1 h. Then NaBH3CN (1.8 g, 28 mmol, 2.0 equiv) was added to the mixture at 50° C. and stirred for 2 h at 85° C. The reaction mixture was quenched with water, extracted with DCM and washed with brine, dried over Na2SO4 and concentrated to obtain crude product. The crude product was purified by silica gel chromatography (DCM:MeOH=40:1) to give the title compound (2.7 g, 50%) as a yellow oil. ESI-MS (M+1)+: 386.2. 1H NMR (400 MHz, CDCl3) δ: 7.72-7.68 (m, 3H), 7.37-7.34 (m, 1H), 7.15-7.10 (m, 2H), 3.94 (s, 2H), 3.81-3.76 (m, 4H), 3.74 (s, 3H), 3.50-3.44 (m, 1H), 1.02 (s, 9H), 0.25 (s, 6H).

Workup

customThe reaction mixture was quenched with water
extractionextracted with DCM
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customto obtain crude product
customThe crude product was purified by silica gel chromatography (DCM:MeOH=40:1)

Sources & evidence

ORD record: ord-4bec657b932b4de6adbcfea019ab5fbc
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802659B2

Reaction notes

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