L-Tartaric acid → Methyl (2-{(R)-(3-Chlorophenyl)[(3r)-1-({(2s)-1-(Methylamino)-3-[(3r)-Tetrahydro-2h-Pyran-3-Yl]propan-2-Yl}carbamoyl)piperidin-3-Yl]methoxy}ethyl)carbamate

HRID 452020Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 452020
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([C@@H:17]2[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:36])[NH:24][C@@H:25]([CH2:29][C@H:30]3[CH2:35][CH2:34][CH2:33][O:32][CH2:31]3)[CH2:26][NH:27][CH3:28])[CH2:18]2)[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:16])[O:14][CH3:15])[CH:5]=[CH:6][CH:7]=1.[C:37]([OH:46])(=[O:45])[C@@H:38]([C@H:40]([C:42]([OH:44])=[O:43])[OH:41])[OH:39]>C(O)C>[C:42]([C@@H:40]([C@H:38]([C:37]([O-:46])=[O:45])[OH:39])[OH:41])([O-:44])=[O:43].[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([C@@H:17]2[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:36])[NH:24][C@@H:25]([CH2:29][C@H:30]3[CH2:35][CH2:34][CH2:33][O:32][CH2:31]3)[CH2:26][NH:27][CH3:28])[CH2:18]2)[O:9][CH2:10][CH2:11][NH:12][C:13](=[O:16])[O:14][CH3:15])[CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 2

HCID 444305L-Tartaric acidHCID 53497561Methyl (2-{(R)-(3-Chlorophenyl)[(3r)-1-({(2s)-1-(Methylamino)-3-[(3r)-Tetrahydro-2h-Pyran-3-Yl]propan-2-Yl}carbamoyl)piperidin-3-Yl]methoxy}ethyl)carbamate

Produkt 2

HCID 119400TartrateHCID 53497561Methyl (2-{(R)-(3-Chlorophenyl)[(3r)-1-({(2s)-1-(Methylamino)-3-[(3r)-Tetrahydro-2h-Pyran-3-Yl]propan-2-Yl}carbamoyl)piperidin-3-Yl]methoxy}ethyl)carbamateAusbeute 111,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
35 °C

Versuchsvorschrift

The free base of methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (0.28 g, 0.53 mmol) and L-tartaric acid (84.4 mg, 0.56 mmol, 99.5%) were dissolved in ethanol (5 mL) to give a clear solution. The solvent was removed in vacuo to dryness, and the residue was redissolved in 95% ethanol:MeCN (3:97 v/v) (10.5 mL) at 35° C. A seed crystal was added and the resulting solution was stirred at 35° C. for 2 hr, then cooled to rt slowly, and stirred for 48 hr. The resulting white crystal was filtered and washed with MeCN (2×5 mL) to give 1:1 L-tartrate of methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (0.31 g, 84%). Selected 1H NMR (CD3OD, 400 MHz), δ: 7.36 (m, 3H), 7.22 (d, 1H), 4.40 (s, 2H), 4.18-4.00 (m, 3H), 3.86 (m, 3H), 3.62 (s, 3H), 3.40 (m, 1H), 3.24 (m, 3H), 3.18-2.84 (m, 5H), 2.72 (s, 3H), 1.90-1.08 (m, 12H); mp=122-127° C. MS ESI +ve m/z 525 (M+1).

Aufarbeitung

  1. customto give a clear solution
  2. customThe solvent was removed in vacuo to dryness
  3. dissolutionthe residue was redissolved in 95% ethanol:MeCN (3:97 v/v) (10.5 mL) at 35° C
  4. additionA seed crystal was added
  5. temperaturecooled to rt slowly
  6. stirringstirred for 48 hr
  7. filtrationThe resulting white crystal was filtered
  8. washwashed with MeCN (2×5 mL)

Quellen und Nachweise

ORD-Eintrag
ord-cdedcce804934444b6a8de781792cb6d
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08487108B2

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