Sodium Bicarbonate → {4-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoic acid ethyl ester

HRID 1794814Notes

Reaction equation

HRID 1794814 reaction equation
C(OC([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)=O)C.[NH2:19][CH2:20][C@@H:21]([C:23]1[CH:24]=[CH:25][C:26]([OH:34])=[C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=1)[OH:22].C(O[BH-](O[C:45](=[O:47])[CH3:46])OC(=O)C)(=O)C.[Na+].[C:49](=O)(O)[O-:50].[Na+]>CN(C)C=O.C(O)(=O)C>[CH2:45]([O:47][C:49](=[O:50])[C:8]1[CH:7]=[CH:6][CH:11]=[CH:10][C:9]=1[N:12]1[CH2:13][CH2:14][CH:15]([NH:19][CH2:20][C@H:21]([OH:22])[C:23]2[CH:24]=[CH:25][C:26]([OH:34])=[C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=2)[CH2:16][CH2:17]1)[CH3:46]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 12717442Ethyl 4-(4-oxopiperidin-1-yl)benzoate

Product 1

HCID 69654607{4-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoic acid ethyl esterYield 50%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

1-(4-Ethoxycarbonylphenyl)-4-piperidone (Taylor, E. C., Skotnicki, J. S. Synthesis, 1981, 606) (29 g, 1.2 mmol) and N-[5-(2-amino-(1R)-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) (0.29 g, 1.2 mmol) were mixed in dimethylformamide (10 mL) and then treated with sodium triacetoxyborohydride (1.01 g, 4.7 mmol) and acetic acid (0.5 mL). After stirring at room temperature under a nitrogen atmosphere for 15 hours the mixture was poured into a saturated aqueous sodium bicarbonate. The precipitate which was formed was collected and purified by silica gel chromatography (methanol/methylene chloride) to give the titled compound as a white solid (0.28 g, 50%); mp>95° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.28 (t, J=7.1 Hz, 3 H), 1.30–1.55 (m, 2 H), 1.80–1.95 (m, 2 H), 2.55–3.50 (m, 5 H), 2.92 (s, 3 H), 3.75–3.90 (m, 2 H), 4.22 (q, J=7.1 Hz, 2 H), 6.82 (d, J=8.2 Hz, 1 H), 6.95 (d, J=8.9 Hz, 2 H), 7.00 (dd, J=8.2, 1.9 Hz, 1 H), 7.18 (d, J=1.9 Hz, 1 H), 7.75 (d, J=8.9 Hz, 2 H); MS (ES) m/z: 478.0 (MH+); HRMS Calcd. for C23H32N3O6S(MH+): 478.2006. Found: 478.2000.

Workup

  1. customThe precipitate which was formed
  2. customwas collected
  3. custompurified by silica gel chromatography (methanol/methylene chloride)

Sources & evidence

ORD record
ord-9a6371cec6bf4ec490248c29e5c6ccad
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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