Methanol → biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino-4-hydroxyphenyl)ethylimino]methyl}-2,5-dimethyl-phenylcarbamoyl)ethyl]piperidin-4-yl ester

HRID 2113275Notes

Reaction equation

HRID 2113275 reaction equation
[CH:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][C:11]([CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([O:21][C:22](=[O:36])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:17][CH2:16]2)=[O:12])=[C:5]([CH3:37])[CH:4]=1)=O.C(O)(=O)C.[NH2:42][CH2:43][C@@H:44]([C:53]1[CH:54]=[CH:55][C:56]([OH:62])=[C:57]([NH:59][CH:60]=[O:61])[CH:58]=1)[O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47].CO>C1(C)C=CC=CC=1>[Si:46]([O:45][C@H:44]([C:53]1[CH:54]=[CH:55][C:56]([OH:62])=[C:57]([NH:59][CH:60]=[O:61])[CH:58]=1)[CH2:43][N:42]=[CH:1][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][C:11]([CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([O:21][C:22](=[O:36])[NH:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:17][CH2:16]2)=[O:12])=[C:5]([CH3:37])[CH:4]=1)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47]

Participants

5

Reactant 3

HCID 887MethanolHCID 46239522Biphenyl-2-ylcarbamic acid 1-[2-(4-formyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl esterHCID 574610645-[(R)-2-amino-1-(tert-butyldimethylsilyloxy)ethyl]-2-hydroxyphenylformamide acetate

Product 1

HCID 86615943biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino-4-hydroxyphenyl)ethylimino]methyl}-2,5-dimethyl-phenylcarbamoyl)ethyl]piperidin-4-yl esterYield 106.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 250 mL round-bottom flask was added biphenyl-2-ylcarbamic acid 1-[2-(4-formyl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (7.1 g, 14.2 mmol) and N-{5-[(R)-2-amino-1-(tert-butyldimethylsilanyloxy)ethyl]-2-hydroxyphenyl}formamide acetic acid salt (5.8 g, 15.6 mmol). Methanol (100 mL) was added to form a slurry and this mixture was stirred at 45° C. to 50° C. under nitrogen for 1 hour. The mixture was then cooled to room temperature and toluene (50 mL) was added and the solvent was removed on a rotary evaporator at temperature ranging from 35° C. to 45° C. Toluene (50 mL) was added to the residue and the solvent was removed to provide biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(tert-butyldimethylsilanyloxy)-2-(3-formylamino-4-hydroxyphenyl)ethylimino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (12 g) as a yellow-orange solid.

Workup

  1. customto form a slurry
  2. customthe solvent was removed on a rotary evaporator at temperature
  3. customranging from 35° C. to 45° C
  4. additionToluene (50 mL) was added to the residue
  5. customthe solvent was removed

Sources & evidence

ORD record
ord-97a85aace26c497384f218c5196733a1
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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