Water → Biphenyl-2-ylcarbamic acid 1-[2-(4-{[(r)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl ester l-tartaric acid salt

HRID 2113277Notes

Reaction equation

HRID 2113277 reaction equation
[Si]([O:8][C@H:9]([C:48]1[CH:53]=[CH:52][C:51]([OH:54])=[C:50]([NH:55][CH:56]=[O:57])[CH:49]=1)[CH2:10][NH:11][CH2:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([NH:20][C:21]([CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][CH:28]([O:31][C:32](=[O:46])[NH:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:27][CH2:26]2)=[O:22])=[C:15]([CH3:47])[CH:14]=1)(C(C)(C)C)(C)C.CC1CCC[O:60]1.F.F.F.C(N([CH2:72][CH3:73])CC)C.[C:74](=[O:77])([OH:76])[O-].[Na+].[OH2:79]>>[C:32]([OH:46])(=[O:31])[C@@H:72]([C@H:73]([C:74]([OH:76])=[O:77])[OH:60])[OH:79].[CH:56]([NH:55][C:50]1[CH:49]=[C:48]([C@@H:9]([OH:8])[CH2:10][NH:11][CH2:12][C:13]2[C:18]([CH3:19])=[CH:17][C:16]([NH:20][C:21]([CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([O:31][C:32](=[O:46])[NH:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[CH2:27][CH2:26]3)=[O:22])=[C:15]([CH3:47])[CH:14]=2)[CH:53]=[CH:52][C:51]=1[OH:54])=[O:57]

Participants

6

Reactant 5

HCID 962WaterHCID 73012-Methyltetrahydrofuran2×HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 86615941biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino-4-hydroxyphenyl)ethylamino]-methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester

Product 1

HCID 86615944Biphenyl-2-ylcarbamic acid 1-[2-(4-{[(r)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl ester l-tartaric acid saltYield 97%

Procedure

To a 200 mL round-bottom flask was added biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino -4-hydroxyphenyl)ethylamino]-methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (3.8 g, 4.8 mmol) and 2-methyltetrahydrofuran (40 mL). The resulting mixture was stirred at room temperature until the ingredients dissolved (about 15 min.) and then triethylamine trihydrofluoride (0.94 mL, 5.76 mmol) was added and the resulting mixture was stirred at 25° C. for about 24 hours. To this mixture was added a 1:1 mixture of saturated aqueous sodium bicarbonate and water (40 mL) and 2-methyltetrahydrofuran and the resulting mixture was stirred until the solid dissolved (solution pH about 8). The layers were separated and the organic layer was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator. The residue was dissolved in 2-methyltetrahydrofuran (50 mL) and solid L-tartaric acid (650 mg) was added. The resulting mixture was stirred at 25° C. to 30° C. for 18 hours and then filtered through filter paper. The filter cake was washed with 2-methyltetrahydrofuran (10 mL), isopropanol (10 mL) and immediately put under vacuum to provide biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl ester L-tartaric acid salt (3.7 g, >97% purity).

Workup

  1. dissolutiondissolved (about 15 min.)
  2. stirringthe resulting mixture was stirred at 25° C. for about 24 hours
  3. additionTo this mixture was added
  4. stirringthe resulting mixture was stirred until the solid
  5. customThe layers were separated
  6. washthe organic layer was washed with brine (30 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated on a rotary evaporator
  10. dissolutionThe residue was dissolved in 2-methyltetrahydrofuran (50 mL)
  11. additionsolid L-tartaric acid (650 mg) was added
  12. stirringThe resulting mixture was stirred at 25° C. to 30° C. for 18 hours
  13. filtrationfiltered
  14. filtrationthrough filter paper
  15. washThe filter cake was washed with 2-methyltetrahydrofuran (10 mL), isopropanol (10 mL)

Sources & evidence

ORD record
ord-19a022502f6f469fabf30376d360e4e6
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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