Methanol → 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

HRID 2113278Notes

Reaction equation

HRID 2113278 reaction equation
C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.[CH:11]([NH:13][C:14]1[CH:15]=[C:16]([C@@H:21]([OH:60])[CH2:22][NH:23][CH2:24][C:25]2[C:30]([CH3:31])=[CH:29][C:28]([NH:32][C:33]([CH2:35][CH2:36][N:37]3[CH2:42][CH2:41][CH:40]([O:43][C:44](=[O:58])[NH:45][C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=4[C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[CH2:39][CH2:38]3)=[O:34])=[C:27]([CH3:59])[CH:26]=2)[CH:17]=[CH:18][C:19]=1[OH:20])=[O:12].CO.C(=O)(O)[O-].[Na+]>O>[CH:11]([NH:13][C:14]1[CH:15]=[C:16]([C@@H:21]([OH:60])[CH2:22][NH:23][CH2:24][C:25]2[C:30]([CH3:31])=[CH:29][C:28]([NH:32][C:33]([CH2:35][CH2:36][N:37]3[CH2:42][CH2:41][CH:40]([O:43][C:44](=[O:58])[NH:45][C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=4[C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[CH2:39][CH2:38]3)=[O:34])=[C:27]([CH3:59])[CH:26]=2)[CH:17]=[CH:18][C:19]=1[OH:20])=[O:12]

Participants

5

Reactant 3

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 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 salt

Product 1

HCID 16755732biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenyl-carbamoyl)ethyl]piperidin-4-yl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 250 mL round-bottom flask was added biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester L-tartaric acid salt (3.5 g) and methanol (35 mL) and the resulting mixture was stirred for 15 min. A 1:1 mixture of saturated aqueous sodium bicarbonate and water (70 mL) was added over a 5 min. period and stirring was continued for 2 hours. The resulting off-white slurry was filtered and the filter cake was washed with water (20 mL), air dried for 2 hours and then dried in a vacuum overnight to provide biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)-ethyl]piperidin-4-yl ester (2.3 g) as a semi-crystalline free base.

Workup

  1. additionwas added over a 5 min. period
  2. stirringstirring
  3. waitwas continued for 2 hours
  4. filtrationThe resulting off-white slurry was filtered
  5. washthe filter cake was washed with water (20 mL), air
  6. customdried for 2 hours
  7. customdried in a vacuum overnight

Sources & evidence

ORD record
ord-8a5ffc66e4b148cbab90e8fc17f6ec9e
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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