Water → HCID 53958027, compound

HRID 1004656Notes

Reaction equation

HRID 1004656 reaction equation
N1[CH:6]=[CH:5][CH:4]=CC=1.[NH2:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[O:14][C@@H:13]([C:18]([O:20]C(C)C)=O)[CH2:12][CH2:11]2.[CH:24]1([CH2:30][CH2:31][CH2:32][N:33]2[C:37](=[O:38])[N:36]([C:39]3[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=3)[N:35]=[N:34]2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[OH2:49].O1CCC[CH2:51]1>C(OCC)(=O)C>[CH2:51]([O:49][C:18]([C@H:13]1[CH2:12][CH2:11][C:10]2[C:15](=[CH:16][CH:17]=[C:8]([NH:7][S:45]([C:42]3[CH:43]=[CH:44][C:39]([N:36]4[C:37](=[O:38])[N:33]([CH2:32][CH2:31][CH2:30][CH:24]5[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]5)[N:34]=[N:35]4)=[CH:40][CH:41]=3)(=[O:47])=[O:46])[CH:9]=2)[O:14]1)=[O:20])[CH:5]([CH3:4])[CH3:6]

Participants

7

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 8028TetrahydrofuranHCID 22471697HCID 22471697, compoundHCID 54211453HCID 54211453, compound

Product 1

HCID 53958027HCID 53958027, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Pyridine (33 mL, 403 mmol) and N,N-dimethylaminopyridine (100 mg) were added to a solution of isopropyl (R)-6-amino-chroman-2-carboxylate (Example 156; 40 g, 161 mmol) and 4-[4-(3-cyclohexyl-propyl)-5-oxo-4,5-dihydro-tetrazol-1-yl]-benzenesulfonyl chloride (Example 157; 62 g, 161 mmol) in tetrahydrofuran (1 L). The reaction mixture was heated to reflux for 12 hours. The mixture was cooled to room temperature and water (200 mL) and ethyl acetate (500 mL) were added. The organic phase was washed with 1 N HCl (3×) followed by brine. The organic phase was dried (sodium sulfate) and concentrated in vacuo. The crude product was chromatographed through a short pad of silica gel (50:50 ethyl acetate/hexane). The resulting solid was mixed with hexane/diethyl ether (90:10) and the mixture filtered to afford a light yellow solid (87 g, 90%). 1H NMR (CDCl3, 300 MHz) δ 8.12 (d, 8.8 Hz, 2 H), 7.80 (d, 8.8 Hz, 2 H), 6.84 (d, 2.6 Hz, 1 H), 6.74 (m, 1 H), 6.66 (m, 1 H), 6.24 (s, 1 H), 4.71 (m, 1 H), 4.0-3.9 (m, 4 H), 2.69 (m, 2 H), 2.18 (m, 2 H), 1.88 (m, 3 H), 1.66 (m, 5 H), 1.22 (m, 6 H), 0.86 (m, 7.0 Hz, 8 H); MS (FAB) m/z 598 (MH+); Rf =0.76 (C).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 12 hours
  3. washThe organic phase was washed with 1 N HCl (3×)
  4. dry with materialThe organic phase was dried (sodium sulfate)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was chromatographed through a short pad of silica gel (50:50 ethyl acetate/hexane)
  7. additionThe resulting solid was mixed with hexane/diethyl ether (90:10)
  8. filtrationthe mixture filtered

Sources & evidence

ORD record
ord-2bf62be65cd4473389b681f9253a3349
Source dataset
uspto-grants-2000_04
Patent number
US06051586

Reaction notes

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