Ethanol → HCID 68535612, compound

HRID 2180199Notes

Reaction equation

HRID 2180199 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH:13]2[CH2:18][C:17]3([C:26]4[C:21](=[CH:22][C:23](Br)=[CH:24][CH:25]=4)[NH:20][CH2:19]3)[CH2:16][CH2:15][N:14]2[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C:10]([NH2:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].[C:38]([C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[CH:44][CH:45]=1)#[N:39].C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.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:1][C:2]1[CH:3]=[C:4]([N:9]([CH:13]2[CH2:18][C:17]3([C:26]4[C:21](=[CH:22][C:23]([C:44]5[CH:43]=[CH:42][CH:41]=[C:40]([C:38]#[N:39])[CH:45]=5)=[CH:24][CH:25]=4)[NH:20][CH2:19]3)[CH2:16][CH2:15][N:14]2[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C:10]([NH2:12])=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 68530500HCID 68530500, compound

Product 1

HCID 68535612HCID 68535612, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of crude 1-(3-chloro-4-fluorophenyl)ureido-6-bromo-1′-benzyloxycarbonyl-spiro[indoline-3,4′-piperidine] (˜0.27 mmol) and Pd(PPh3)4 (0.011 g, 0.030 mmol, 10 mol %) in degassed toluene (5 mL) was added a solution of 3-cyanophenylboronic acid (0.067 g, 0.46 mmol, 1.7 eq.), aqueous Na2CO3 (2.5 mL of a 2N solution, 5 mmol), and EtOH (2.5 mL). The resulting mixture was heated at 90° C. for 16 h then partitioned between EtOAc (20 mL) and 10% aqueous NaHCO3 (20 mL). The organic phase was separated and washed with 10% aqueous NaHCO3 (3×10 mL) and saturated brine (10 mL), dried over Na2SO4, filtered and concentrated by rotary evaporation. The crude residue was purified by flash column chromatography by eluting 10-20% EtOAc/hexane to give 1-(3-chloro-4-fluorophenyl)ureido-6-(3-cyanophenyl)-1′-benzyloxycarbonyl-spiro[indoline-3,4′-piperidine] as a yellowish oil (0.057 g, 0.097 mmol, 36%). 1H NMR (300 MHz, CD3OD): δ 7.23 to 8.31 (m, 15H), 5.27 (s, 2H), 4.32 (d, 2H), 4.21 (s, 2H), 3.17 (m, 2H), 1.98 (m, 2H), 1.82 (m, 2H).

Workup

  1. customthen partitioned between EtOAc (20 mL) and 10% aqueous NaHCO3 (20 mL)
  2. customThe organic phase was separated
  3. washwashed with 10% aqueous NaHCO3 (3×10 mL) and saturated brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customThe crude residue was purified by flash column chromatography
  8. washby eluting 10-20% EtOAc/hexane

Sources & evidence

ORD record
ord-33494a47f1494635ae1c12fcbc886f9c
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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