Triethylamine → tert-Butyl (1-(2-hydroxypropyl)piperidin-4-yl)carbamate

HRID 255389Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.Br[CH2:16][CH:17]([OH:19])[CH3:18].BrC(C)CO.C(N(CC)CC)C>C(#N)C>[OH:19][CH:17]([CH3:18])[CH2:16][N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5][CH2:6]1

Participants

Conditions

Temperature: 70 °C

Procedure

tert-Butyl piperidin-4-ylcarbamate (2.0 g, 10.0 mmol), 1-bromopropan-2-ol (2.8 g, 20.0 mmol, commercial product which also contained 30% of the regioisomer 2-bromopropan-1-ol), triethylamine (4.2 mL, 30.0 mmol), and acetonitrile (15 mL) were combined in a microwave vial and heated to 70° C. for 4 hours. The reaction mixture was concentrated to dryness. The crude product was partitioned between ethyl acetate/water. The aqueous phase was re-extracted 2× with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. The product was purified by flash chromatography on silica gel eluting with a gradient of 20-30% methanol in dichloromethane to give 1.7 g of the desired product as an oil.

Workup

concentrationThe reaction mixture was concentrated to dryness
customThe crude product was partitioned between ethyl acetate/water
extractionThe aqueous phase was re-extracted 2× with ethyl acetate
dry with materialThe combined organic phases were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated to dryness
customThe product was purified by flash chromatography on silica gel eluting with a gradient of 20-30% methanol in dichloromethane

Sources & evidence

ORD record: ord-3e11c137c99a4ccb942b1c74a5e055d9
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875715B2

Reaction notes

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