1,1'-Carbonyldiimidazole → methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452017Notes

Reaction equation

HRID 452017 reaction equation
[NH2:1][C@@H:2]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.CCN(C(C)C)C(C)C.[CH3:43][O:44][C:45](=[O:64])[NH:46][CH2:47][CH2:48][O:49][CH:50]([C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[CH:58]=1)[CH:51]1CCCN[CH2:52]1>C(Cl)Cl>[F:63][C:59]1[CH:58]=[C:57]([C@@H:50]([C@@H:51]2[CH2:52][CH2:31][CH2:30][N:29]([C:27](=[O:28])[NH:1][C@@H:2]([CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:33]2)[O:49][CH2:48][CH2:47][NH:46][C:45](=[O:64])[O:44][CH3:43])[CH:62]=[CH:61][CH:60]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 67365379{2-[(3-Fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl esterHCID 673661002-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate

Product 1

HCID 67365837methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamateYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (300 mg, 0.95 mmol) and CDI (154 mg, 0.95 mmol) in anhydrous CH2Cl2 (20 mL), DIEA (612 mg, 4.7 mmol) was added with ice bath. After addition, the mixture was stirred for 1 h at 0° C., then was added to a solution of {2-[(3-fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl ester (245 mg, 0.79 mmol) in anhydrous CH2Cl2 (25 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by preparative TLC to afford methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (258 mg, 50% yield).

Workup

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by preparative TLC

Sources & evidence

ORD record
ord-d56fe6c0cd0842a4bb343eaf5e3fe4d3
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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