Water → 4-(4-Ethoxycarbonyl-thiophen-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1809098Notes

Reaction equation

HRID 1809098 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8](Br)[S:9][CH:10]=1)=[O:5])[CH3:2].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH:23]=[C:22](B2CC(C)(C)C(C)(C)C2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].O.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:12]([O:16][C:17]([N:19]1[CH2:20][CH:21]=[C:22]([C:8]2[S:9][CH:10]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:7]=2)[CH2:23][CH2:24]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 15293216Ethyl 5-bromothiophene-3-carboxylateHCID 68758613tert-butyl 4-(3,3,4,4-tetramethylborolan-1-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 595425874-(4-Ethoxycarbonyl-thiophen-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 56.3%

Reagents, catalysts & solvents 2

HCID 178420534HCID 178420534, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

2-Bromothiophene-4-carboxylic acid ethyl ester (1.0 g, 5.26 mmol) and 4-(3,3,4,4-tetramethyl-borolan-1-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (5.26 mmol) were dissolved in DME (40 mL), IMS (20 mL) and water (10 mL). Palladium tetrakis-triphenylphoshine (0.53 mmol) and caesium carbonate (7.9 mmol) were then added and the mixture heated to 120° C. for 20 minutes using microwave radiation. The solvent was then evaporated and the residue purified by flash chromatography on silica, eluting with 0-40% ethyl acetate in cyclohexane. The fractions containing the desired product were combined and evaporated to give the title compound as a clear oil (1.0 g). LCMS m/z 238.06 [M+H]+ RT=4.33min (Analytical Method 4).

Workup

  1. customThe solvent was then evaporated
  2. customthe residue purified by flash chromatography on silica
  3. washeluting with 0-40% ethyl acetate in cyclohexane
  4. additionThe fractions containing the desired product
  5. customevaporated

Sources & evidence

ORD record
ord-7882d512d5f64a5287386568f78cc60e
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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