Ethanol → HCID 86669264, compound

HRID 2366922Notes

Reaction equation

HRID 2366922 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:17][CH:18]([O:20][C:21](=[O:39])[NH:22][CH2:23][C@H:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31](Br)[CH:32]=2)[N:27]([C:35](=[O:37])[CH3:36])[C@@H:26]([CH3:38])[CH2:25]1)[CH3:19].C(=O)([O-])[O-].[K+].[K+].C(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.C1(C)C=CC=CC=1>[CH:21]([OH:39])=[O:20].[C:35]([N:27]1[C:28]2[C:33](=[CH:32][C:31]([C:11]3[CH:12]=[CH:13][C:8]([CH2:7][N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:9][CH:10]=3)=[CH:30][CH:29]=2)[C@H:24]([CH2:23][NH:22][C:21](=[O:39])[O:20][CH:18]([CH3:17])[CH3:19])[CH2:25][C@@H:26]1[CH3:38])(=[O:37])[CH3:36]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 23005343HCID 23005343, compoundHCID 86669266HCID 86669266, compound

Product 1

HCID 86669264HCID 86669264, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

[4-(1-Piperidinylmethyl)phenyl]boronic acid (135 mg, 0.475 mmol), 1-methylethyl[(cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]methylcarbamate (for a preparation see Intermediate 40) (104 mg, 0.271 mmol), Tetrakis(triphenylphosphine)palladium(0) (15.68 mg, 0.014 mmol) and potassium carbonate (150 mg, 1.085 mmol) were placed in a round-bottomed flask with ethanol (1.8 mL) and Toluene (1.800 mL). The reaction mixture was stirred at 90° C. under N2 overnight. The brown reaction mixture was concentrated down and partitioned between EtOAc (10 mL) and water (10 mL). Further EtOAc (15 mL) was used to extract the product from the aqueous layer and the organics were combined, washed with saturated sodium bicarbonate solution (10 mL), dried (phase separator) and concentrated to yield a brown oil. This was purified by SP4 on a 12+M silica column using a gradient of 0.6-6% 2M methanolic ammonia in DCM. The relevant fractions were concentrated down to obtain a yellow oil (121 mg). Further purification was carried out using MDAP to give the desired compound (70 mg). LCMS (Method B): Rt=0.73, MH+=478

Workup

  1. concentrationThe brown reaction mixture was concentrated down
  2. custompartitioned between EtOAc (10 mL) and water (10 mL)
  3. extractionto extract the product from the aqueous layer
  4. washwashed with saturated sodium bicarbonate solution (10 mL)
  5. customdried (phase separator)
  6. concentrationconcentrated
  7. customto yield a brown oil
  8. customThis was purified by SP4 on a 12+M silica column
  9. concentrationThe relevant fractions were concentrated down

Sources & evidence

ORD record
ord-4a42e87f926d456fbbdd4a0350661cc3
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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