Formaldehyde → Tert-butyl 4-(4-hydroxybut-2-yn-1-yl)piperidine-1-carboxylate

HRID 1798796Notes

Reaction equation

Br[C:2](Br)=[CH:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[Li]CCCC.[CH2:24]=[O:25].[Cl-].[NH4+]>C1COCC1>[OH:25][CH2:24][C:2]#[C:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1

Participants

Conditions

Temperature: -78 °C

Procedure

tert-Butyl 4-(3,3-dibromoprop-2-en-1-yl)piperidine-1-carboxylate from step 1 of this Example (19.5 g, 50.9 mmol) was dissolved in THF (170 mL) and cooled to −78° C. n-BuLi (2.5 Min hexanes, 46.8 mL, 117 mmol) was added slowly, maintaining internal temperature below −65° C. The mixture was stirred for additional 30 min, before paraformaldehyde (4.59 g, 152.7 mmol) was added in one portion. The reaction was stirred at −78° C. for 30 min and warmed to room temperature and allowed to stir at RT for 1 hour. Saturated aqueous ammonium chloride was added, and the aqueous layer was extracted 3 times with ethyl acetate. Column chromatography eluting with 30% acetone/hexanes afforded the product as colorless oil.

Workup

additionwas added slowly
temperaturemaintaining internal temperature below −65° C
additionwas added in one portion
temperaturewarmed to room temperature
stirringto stir at RT for 1 hour
extractionthe aqueous layer was extracted 3 times with ethyl acetate
washColumn chromatography eluting with 30% acetone/hexanes

Sources & evidence

ORD record: ord-cb2b4d36021944d896eaa603975644f3
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08343990B2

Reaction notes

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