Water → HCID 178497512, compound

HRID 415988Notes

Reaction equation

HRID 415988 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@H:14]2[CH2:19][CH2:18][C@@H:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].[CH3:41][O:42][C:43]([C:45]1[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=1)=[O:44].C(=O)([O-])[O-].[Na+].[Na+].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.O1CCCC1>[CH3:41][O:42][C:43]([C:45]1[CH:50]=[CH:49][C:48]([C:4]2[CH:5]=[C:6]([Cl:32])[C:7]([CH2:8][C@@H:9]3[CH2:13][CH2:12][N:11]([C@H:14]4[CH2:15][CH2:16][C@@H:17]([O:20][Si:21]([CH:22]([CH3:23])[CH3:24])([CH:25]([CH3:26])[CH3:27])[CH:28]([CH3:29])[CH3:30])[CH2:18][CH2:19]4)[C:10]3=[O:31])=[C:2]([Cl:1])[CH:3]=2)=[CH:47][CH:46]=1)=[O:44]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 178460991HCID 178460991, compound

Product 1

HCID 178497512HCID 178497512, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Bubble nitrogen through a mixture of trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-cis-1-(4-triisopropylsilanyloxy-cyclohexyl)-pyrrolidin-3-ylmethyl]-phenyl ester (12.2 g, 18.87 mmol), 4-methoxycarbonylphenylboronic acid (4.1 g, 22.64 mmol), sodium carbonate (6 g, 56.6 mmol), 50 mL water, and 150 mL tetrahydrofuran for 30 min at room temperature. Add tetrakis(triphenylphosphine)palladium (1.7 g, 1.47 mmol) by weighing into a nitrogen filled vial and transferring the material as a dry solid to the reaction flask. Sparge an additional 5 min, then heat at 80° C. 1 hr. Dilute with 50 mL each of water and ethyl acetate, separate layers and extract the aqueous layer with 25 mL ethyl acetate. After combining the organic layers, wash with 50 mL brine, dry over magnesium sulfate and concentrate under vacuum. Purify on silica by eluting with 10-30% ethyl acetate in hexanes to give 11.1 g (93%) of product as an ivory foam: MS (m/z): 632 (M+).

Workup

  1. customBubble nitrogen
  2. customSparge an additional 5 min
  3. custom1 hr
  4. additionDilute with 50 mL each of water and ethyl acetate
  5. customseparate layers
  6. extractionextract the aqueous layer with 25 mL ethyl acetate
  7. washwash with 50 mL brine
  8. dry with materialdry over magnesium sulfate
  9. concentrationconcentrate under vacuum
  10. customPurify on silica
  11. washby eluting with 10-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-dab4d071dc02446398b4085fd14874a8
Source dataset
uspto-grants-2012_01
Patent number
US08088776B2

Reaction notes

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