Potassium Phosphate, Tribasic → Ethyl 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoate

HRID 1942704Notes

Reaction equation

HRID 1942704 reaction equation
[CH2:1]([C:3]1[C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]1)[CH3:2].Br[C:33]1[N:37]=[C:36]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH:45]([CH3:47])[CH3:46])=[C:40]([Cl:48])[CH:39]=2)[S:35][N:34]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C.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>[Cl:48][C:40]1[CH:39]=[C:38]([C:36]2[S:35][N:34]=[C:33]([C:8]3[C:3]([CH2:1][CH3:2])=[C:4]([CH2:18][CH:19]4[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]4)[CH:5]=[CH:6][CH:7]=3)[N:37]=2)[CH:43]=[CH:42][C:41]=1[O:44][CH:45]([CH3:46])[CH3:47]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 584940863-Bromo-5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazoleHCID 58494099HCID 58494099, compound

Product 1

HCID 58494103Ethyl 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoateYield 37.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of ethyl 3-(4-{[2-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinyl)propanoate (D140) (1.3 g, 3.03 mmol) in N,N-Dimethylformamide (DMF) (6 mL) and Water (1.500 mL) was added 3-bromo-5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazole (D43) (1.010 g, 3.03 mmol), tripotassium phosphate (1.928 g, 9.08 mmol) and Pd(Ph3P)4 (0.350 g, 0.303 mmol). The reaction mixture was heated by Biotage Initiator to 120° C. for 20 min. The reaction mixture was diluted with ethyl acetate, washed with water, dried and concentrated and purified by ISCO column chromatography to afford ethyl 3-(4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)propanoate (D141) (0.63 g). MS (ES): C30H38ClN3O3S requires 555.2. found 556.2 (M+H+).

Workup

  1. washwashed with water
  2. customdried
  3. concentrationconcentrated
  4. custompurified by ISCO column chromatography

Sources & evidence

ORD record
ord-5bd6bee7b14840f5b8c095be0f95e946
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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