Acetic Acid → Methyl 1-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]cyclobutanecarboxylate

HRID 733092Notes

Reaction equation

[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[CH:16]([C:18]1([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19]1)=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>O1CCCC1>[C:1]([O:5][C:6]([NH:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([CH2:16][C:18]2([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19]2)[CH2:13][CH2:14]1)=[O:15])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred mixture of tert-butyl(piperidin-4-ylmethyl)carbamate (12.8 g, 60 mmol) and methyl 1-formylcyclobutanecarboxylate (2.13 g, 15 mmol, Davis, Charles R.; Swenson, Dale C.; Burton, Donald J., J. Org. Chem., 1993, 58, 6843) in tetrahydrofuran (50 mL) was added acetic acid (8.6 mL, 150 mmol) at ambient temperature. After 30 min, sodium triacetoxyborohydride (12.7 g, 60 mmol) was added to the mixture. Then, the mixture was heated to 60° C. for 2 h. After cooling, the reaction mixture was poured into sat. NaHCO3 aq. The aqueous layer was extracted with CH2Cl2 for 3 times. The combined organic phase were washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (1:1) to give 4.25 g (83%) of the title compound as white solid.

Workup

temperatureAfter cooling
extractionwas extracted with CH2Cl2 for 3 times
washThe combined organic phase were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record: ord-7d351ffb7d2645e6b188a7254df7a931
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07589109B2

Reaction notes

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