Methanol → (S)-tert-Butyl 2-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate

HRID 418038Notes

Reaction equation

HRID 418038 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][C:15]([OH:17])=[O:16])=[O:7])([CH3:4])[CH3:3].[CH3:18]CN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CO>[Cl-].[Na+].O.CN(C=O)C>[CH3:18][O:16][C:15](=[O:17])[CH2:14][C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 15142762-[(2S)-1-[(tert-butoxy)carbonyl]piperidin-2-yl]acetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 10264438(S)-tert-Butyl 2-(2-methoxy-2-oxoethyl)piperidine-1-carboxylateYield 95.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Into a 250 ml round bottom flask ((2S)-1-{[(1,1-dimethylethyl)oxy]carbonyl}-2-piperidinyl)acetic acid (1.00 g, 4.11 mmol), DMF (25 ml), DIPEA (2.15 ml, 12.33 mmol) and TBTU (1.98 g, 6.17 mmol) were added. The mixture was stirred at rt for 20 min and a brown colour was formed. After this time MeOH (0.25 ml, 6.17 mmol) was added and the resulting solution stirred at rt for 30 min. Then it was transferred into e separatory funnel containing brine (20 ml) and extracted with EtOAc (20 ml×2), the combined organic layers were washed with water/ice (5×20 ml). The organic layer was dried (Na2SO4), filtered and concentrated. The crude obtained was purified by column chromatography (Biotage SP1, Cy-EtOAc from 100/0 to 85/15). Collected fractions gave the title compound (1.01 g, 3.92 mmol, 95% yield) as a colorless oil. 1H-NMR (500 MHz, CDCl3) δ(ppm): 4.67-4.75 (m, 1H), 3.96-4.05 (m, 1H), 3.67 (s, 3H), 2.79 (t, 1H), 2.61 (dd, 1H), 2.53 (dd, 1H), 1.60-1.70 (m, 6H), 1.46 (s, 9H).

Workup

  1. customa brown colour was formed
  2. stirringthe resulting solution stirred at rt for 30 min
  3. customThen it was transferred into e separatory funnel
  4. extractionextracted with EtOAc (20 ml×2)
  5. washthe combined organic layers were washed with water/ice (5×20 ml)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude obtained
  10. customwas purified by column chromatography (Biotage SP1, Cy-EtOAc from 100/0 to 85/15)

Sources & evidence

ORD record
ord-1f4f18c7d95741f6af68152f035c2c0c
Source dataset
uspto-grants-2012_01
Patent number
US08093255B2

Reaction notes

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