Sodium hydride → HCID 118021981, compound

HRID 575803Notes

Reaction equation

HRID 575803 reaction equation
[F:1][C:2]1([F:9])[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].[CH2:12]([S:14]([C:17]1[CH:18]=[CH:19][C:20](F)=[C:21]([C:23]2[N:28]3[CH:29]=[N:30][CH:31]=[C:27]3[C:26](=[O:32])[N:25]([CH3:33])[CH:24]=2)[CH:22]=1)(=[O:16])=[O:15])[CH3:13]>C1COCC1>[F:1][C:2]1([F:9])[CH2:7][CH2:6][CH:5]([O:8][C:20]2[CH:19]=[CH:18][C:17]([S:14]([CH2:12][CH3:13])(=[O:16])=[O:15])=[CH:22][C:21]=2[C:23]2[N:28]3[CH:29]=[N:30][CH:31]=[C:27]3[C:26](=[O:32])[N:25]([CH3:33])[CH:24]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5463004,4-Difluorocyclohexan-1-olHCID 118021875HCID 118021875, compound

Product 1

HCID 118021981HCID 118021981, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4,4-difluorocyclohexan-1-ol (162 mg, 1.19 mmol) in THF (10 mL) was added NaH (48 mg, 1.19 mmol, 60% in mineral oil) in one portion at 25° C. under N2. The mixture was stirred at 25° C. for 30 minutes. Then the title compound from Step 2 (200 mg, 0.6 mmol) was added and the mixture was stirred at 25° C. for 18 hours. The reaction contents were poured into ice-water (v/v=1/1) (150 mL) and stirred for 20 minutes. The aqueous phase was extracted with EA (40 mL×3). The combined organic phase was washed with brine (20 mL×2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to afford the title compound (57.35 mg, 22%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.63 (s, 1H), 8.26 (s, 1H), 8.04 (dd, J1=8.8 Hz, J 2=2.4 Hz 1H), 7.95 (d, J=2.4 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 7.31 (s, 1H), 4.90-4.84 (brs, 1H), 3.44 (s, 3H), 3.32 (q, J=7.2 Hz, 2H), 1.85-1.83 (m, 4H), 1.69-1.61 (m, 4H), 1.15 (t, J=7.2 Hz, 3H). LCMS: 452.2 (M+H)+

Workup

  1. stirringthe mixture was stirred at 25° C. for 18 hours
  2. customThe reaction contents
  3. stirringstirred for 20 minutes
  4. extractionThe aqueous phase was extracted with EA (40 mL×3)
  5. washThe combined organic phase was washed with brine (20 mL×2)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-c46781f04f0546adb99501d47ade4fa0
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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