Sodium Bicarbonate → [5-(5-{1-[4-(methylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazol-2-yl]methanol

HRID 1882101Notes

Reaction equation

HRID 1882101 reaction equation
[Si]([O:18][CH2:19][C:20]1[S:24][C:23]([C:25](=O)[CH2:26][CH2:27][C:28](=O)[CH:29]([C:37]2[CH:42]=[CH:41][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:39][CH:38]=2)[CH2:30][CH:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[N:22][N:21]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])(=O)C.[NH4+:53].C(=O)([O-])O.[Na+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(O)(=O)C.C(OCC)(=O)C.O1CCCC1>[CH3:46][S:43]([C:40]1[CH:41]=[CH:42][C:37]([CH:29]([C:28]2[NH:53][C:25]([C:23]3[S:24][C:20]([CH2:19][OH:18])=[N:21][N:22]=3)=[CH:26][CH:27]=2)[CH2:30][CH:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[CH:38][CH:39]=1)(=[O:45])=[O:44]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 2724141Tetrabutylammonium FluorideHCID 593315211-[5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3,4-thiadiazol-2-yl]-5-[4-(methylsulfonyl)phenyl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione

Product 1

HCID 136166648[5-(5-{1-[4-(methylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3,4-thiadiazol-2-yl]methanolYield 81%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 1-[5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-1,3,4-thiadiazol-2-yl]-5-[4-(methylsulfonyl)phenyl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione (1.95 g) in acetic acid (20 mL) was added ammonium acetate (3.41 g), and the mixture was stirred at 110° C. for 30 min. The reaction mixture was cooled to room temperature, and neutralized with saturated aqueous sodium hydrogen carbonate solution. The reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated to give a crude product (1.9 g). To a solution of the obtained crude product in tetrahydrofuran (10 mL) was added tetrabutylammonium fluoride (1M tetrahydrofuran solution) (5 mL) at room temperature. The reaction mixture was stirred at room temperature for 10 min and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (1.0 g, yield 81%) was obtained as white crystals from a fraction eluted with ethyl acetate. melting point 199-201° C. MS: 448 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give a crude product (1.9 g)
  7. stirringThe reaction mixture was stirred at room temperature for 10 min
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b0a320c3067b4760a27f03b8739b857d
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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