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

HRID 713926Notes

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-6754d25f99804043a861718aef1af0a6
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09186367B2

Reaction notes

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