Sodium Carbonate → HCID 178463239, compound

HRID 1527788Notes

Reaction equation

HRID 1527788 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:13]([C@H:16]2[CH2:21][CH2:20][C@H:19]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:17]2)[CH2:14][CH3:15])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[OH:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[C:26]([O:25][C:23]([NH:22][C@H:19]1[CH2:20][CH2:21][C@H:16]([N:13]([CH2:14][CH3:15])[C:4]2[C:5]([CH3:12])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:11]=[C:2]([C:34]3[CH:35]=[CH:36][C:31]([OH:30])=[CH:32][CH:33]=3)[CH:3]=2)[CH2:17][CH2:18]1)=[O:24])([CH3:28])([CH3:27])[CH3:29]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 178463215HCID 178463215, compound

Product 1

HCID 178463239HCID 178463239, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of methyl 5-bromo-3-(((trans)-4-((tert-butoxycarbonyl)amino)cyclohexyl)(ethyl)amino)-2-methylbenzoate (10 g, 21.3 mmol, see, e.g., WO2012142504) and (4-hydroxyphenyl)boronic acid (3.5 g, 25.3 mmol) in a mixture of dioxane (225 mL) and water (75 mL), Na2CO3 (8.01 g, 75.5 mmol) was added and the solution was purged with argon for 30 min. Then Pd(PPh3)4 (2.4 g, 2.07 mmol) was added and argon was purged again for another 15 min. Reaction mass was heated at 100° C. for 4 h. On completion, reaction mixture was diluted with water and extracted with ethyl acetate. Combined organic layer was dried over sodium sulfate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the title compound (8.9 g, 87% yield).

Workup

  1. additionwas added
  2. customthe solution was purged with argon for 30 min
  3. customargon was purged again for another 15 min
  4. customReaction mass
  5. customOn completion, reaction mixture
  6. extractionextracted with ethyl acetate
  7. dry with materialCombined organic layer was dried over sodium sulfate
  8. customRemoval of the solvent under reduced pressure
  9. customfollowed by column chromatographic purification

Sources & evidence

ORD record
ord-e17d0b66809e4bcfba7d1311af422b43
Source dataset
uspto-grants-2015_07
Patent number
US09089575B2

Reaction notes

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