Propanoic acid, 2-bromo-2-methyl-, ethyl ester → HCID 59253182, compound

HRID 1809392Notes

Reaction equation

HRID 1809392 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:14]C(=O)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].Br[C:21]([CH3:28])([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])([CH3:28])[CH3:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 14797Potassium HydroxideHCID 22494773tert-Butyl 4-(acetylthio)piperidine-1-carboxylate

Product 1

HCID 59253182HCID 59253182, compoundYield 91,259.898%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 5.41 g (0.02 mmol) of 4-acetylsulfanyl-piperidine-1-carboxylic acid tert-butyl ester in ethanol (50 mL) is degassed with nitrogen over 0.5 h and 2.34 g (0.04 mol) of KOH are added, followed by 8.14 g (0.04 mol) of ethyl α-bromoisobutyrate. The reaction is stirred for 18 h at room temperature under a nitrogen atmosphere. The reaction mixture is concentrated under reduced pressure. The residue is partitioned between DCM (100 mL) and water (100 mL). The organic layer is washed with water (50 mL), brine (250 mL), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure and purified by column chromatography (silica, eluent heptanes, 50% ethyl acetate) to afford 6.05 g of 4-(1-ethoxycarbonyl-1-methyl-ethylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester as a brown oil. Yield: 87%; ES-MS: m/z 354 [M+Na], 232 [[M+H—C5H9O2]; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.25-1.35 (3H, m), 1.46 (9H, s), 1.48-1.53 (2H, m), 1.55 (6H, s), 1.88 (2H, dd, J=13.31, 3.47 Hz), 2.94-3.04 (3H, m), 3.81-3.92 (2H, m), 4.19 (2H, q, J=7.10 Hz)

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. customThe residue is partitioned between DCM (100 mL) and water (100 mL)
  3. washThe organic layer is washed with water (50 mL), brine (250 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. custompurified by column chromatography (silica, eluent heptanes, 50% ethyl acetate)

Sources & evidence

ORD record
ord-bcab174352d04020854ae0b9660a65d4
Source dataset
uspto-grants-2013_01
Patent number
US08362039B2

Reaction notes

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