Potassium Carbonate → 4-[3-Methoxy-5-(3-methoxycarbonyl-propoxy)-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 502430Notes

Reaction equation

HRID 502430 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:25])[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([OH:24])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].OC1C=C(C=C(OC)C=1)C(O)=O.C(OC(N1CCC(N)CC1)=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])[O-].[K+].[K+].[CH3:70][O:71][C:72](=[O:77])[CH2:73][CH2:74][CH2:75]Br>CN(C1C=CN=CC=1)C.ClCCl.O1CCCC1.CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15](=[O:25])[C:16]2[CH:17]=[C:18]([O:24][CH2:75][CH2:74][CH2:73][C:72]([O:71][CH3:70])=[O:77])[CH:19]=[C:20]([O:22][CH3:23])[CH:21]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 6

HCID 11430Potassium CarbonateHCID 107604Methyl 4-bromobutyrateHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 74720243-Hydroxy-5-methoxybenzoic acidHCID 684587374-(3-Hydroxy-5-methoxy-benzoylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 684598954-[3-Methoxy-5-(3-methoxycarbonyl-propoxy)-benzoylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 92.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

1.60 g (4.6 mmol) of 4-(3-hydroxy-5-methoxy-benzoylamino)-piperidine-1-carboxylic acid tert-butyl ester [prepared from 3-hydroxy-5-methoxy-benzoic acid by reaction with 4-amino-piperidine-carboxylic acid tert-butyl ester, N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride and N,N-dimethyl-4-aminopyridine in dichloromethane/tetrahydrofuran between 0° C. and rt in analogy to example 60d)] was dissolved in 65 mL of MeCN at rt; 1.29 g (9.4 mmol) of anhydrous potassium carbonate was added at 5° C.; then, 0.61 mL (0.87 g=4.8 mmol) of 4-bromo-butyric acid methyl ester was added drop by drop. The reaction mixture was stirred at 95° C. for 22 hours. It was then cooled down to ambient temperature, poured into crashed ice and extracted twice with EtOAc. The organic phases were washed with water and brine, dried over MgSO4, filtered and evaporated i.V. to yield 1.91 g of the title compound as colorless solid. MS: 451.1 (MH+).

Workup

  1. temperatureIt was then cooled down to ambient temperature
  2. additionpoured
  3. extractionextracted twice with EtOAc
  4. washThe organic phases were washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated i.V

Sources & evidence

ORD record
ord-217780d8a3ba41b7aa8b98371c766628
Source dataset
uspto-grants-2010_08
Patent number
US07772253B2

Reaction notes

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