Ammonium Chloride → HCID 90253453, compound

HRID 1478709Notes

Reaction equation

HRID 1478709 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][CH:12]([C@@H:14]1[O:32][CH2:31][C@:17]2([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=3[F:40])[N:18]=[C:19]([NH:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[S:20][CH2:21][C@@H:16]2[CH2:15]1)[OH:13])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[F:40][C:34]1[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=1[C@:17]12[CH2:31][O:32][C@@H:14]([CH:12]([OH:13])[CH2:11][CH2:10][CH2:9][OH:8])[CH2:15][C@H:16]1[CH2:21][S:20][C:19]([NH:22][C:23](=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[N:18]2

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 90253448HCID 90253448, compound

Product 1

HCID 90253453HCID 90253453, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

N-[(4aR,6R,8aS)-6-(4-{[tert-Butyl(dimethyl)silyl]oxy}-1-hydroxybutyl)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C11) (28 mg, 47 μmol) was dissolved in tetrahydrofuran (0.3 mL) and cooled to 0° C. A solution of tetrabutylammonium fluoride in tetrahydrofuran (1 M, 61 μL, 61 μmol) was added drop-wise, and the reaction mixture was allowed to warm to room temperature and then stir for 1 hour. After addition of saturated aqueous ammonium chloride solution, the mixture was extracted with ethyl acetate (3×5 mL); the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via chromatography on silica gel (Gradient: 35% to 100% ethyl acetate in heptane) provided the product as a white foam. Yield: 19 mg, 40 μmol, 85%. LCMS m/z 477.2 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.22 (br d, J=7.4 Hz, 2H), 7.49-7.56 (m, 1H), 7.42-7.49 (m, 2H), 7.39 (ddd, J=9.0, 9.0, 6.3 Hz, 1H), 6.85-6.97 (m, 2H), 4.16 (dd, J=12.1, 1.4 Hz, 1H), 3.85 (br d, J=12.1 Hz, 1H), 3.53-3.74 (m, 4H), 3.10-3.19 (m, 1H), 3.02 (dd, J=12.9, 4.1 Hz, 1H), 2.65 (dd, J=12.9, 2.5 Hz, 1H), 1.94-2.06 (m, 1H), 1.63-1.80 (m, 4H), 1.49-1.60 (m, 1H).

Workup

  1. temperatureto warm to room temperature
  2. extractionthe mixture was extracted with ethyl acetate (3×5 mL)
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification via chromatography on silica gel (Gradient: 35% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e21e64b5e9924b1d9ebb35f7ec6c177a
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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