Sodium Bicarbonate → HCID 86724089, compound

HRID 1748747Notes

Reaction equation

HRID 1748747 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][C:14]([CH3:17])([CH3:16])[CH2:13][NH:12][C:11]2[N:18]([CH3:22])[N:19]=[C:20]([CH3:21])[C:10]1=2.[CH2:23]1[O:25][CH:24]1[C:26]([F:29])([F:28])[F:27].[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.C(=O)(O)[O-].[Na+]>C(#N)C.CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][C:14]([CH3:17])([CH3:16])[CH2:13][N:12]([CH2:23][CH:24]([OH:25])[C:26]([F:29])([F:28])[F:27])[C:11]2[N:18]([CH3:22])[N:19]=[C:20]([CH3:21])[C:10]1=2

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 136216145HCID 136216145, compound

Product 1

HCID 86724089HCID 86724089, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine (0.1 g, 0.28 mmol, Ex. D.4), dissolved in dry acetonitrile/DMF (4:1, 5 mL), was added 3,3,3-trifluoro-1,2-propenoxide (0.5 mL, 5.45 mmol) and ytterbium triflate (0.05 g, 0.4 mmol). The reaction mixture was stirred, for about 72 h, at about 50° C. After cooling to rt, 5% aqueous sodium bicarbonate (25 mL) and ethyl acetate (25 mL) were added. The layers were separated and the organic layer was washed with water (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate/methanol/acetic acid (8:2:0.1) followed by ethyl acetate/methanol/acetic acid (5:5:0.1)), to afford crude product which was purified by prep-HPLC (Table 2, Method c) to yield 3-[4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,7-dihydropyrazolo[3,4-e][1,4]thiazepin-8-yl]-1,1,1-trifluoro-propan-2-ol (0.077 g, 0.16 mmol, 58%), as a white solid: LC-MS (Table 1, Method a) Rt=2.71 min, m/z 468 (M+H)+; 1H NMR (400 MHz, CDCl3, diastereomer mixture, ratio A:B=54:46) δ ppm 1.04 (3 H, s) 1.38 (3 H, s) 1.87 (3 H, s) 3.43 (1 H, dd, J=14.7, 6.1 Hz) 3.65-3.75 (1 H, m) 4.07 (3 H, s) 4.11-4.28 (2 H, m) 4.41-4.50 (1 H, m) 5.22 (1 H, s) 7.30 (1 H, dd, J=8.3, 2.2 Hz) 7.46 (1 H, d, J=2.2 Hz) 7.50 (1 H, d, J=8.3 Hz) 8.93 (1H, t, J=4.8 Hz) (Isomer A); 1H NMR (400 MHz, CDCl3) δ ppm 1.01 (3 H, s) 1.36 (3 H, s) 1.90 (3 H, s) 3.37 (1 H, dd, J=14.6, 7.1 Hz) 3.65-3.75 (1 H, m) 3.98 (3 H, s) 4.11-4.28 (2 H, m) 4.50-4.60 (1 H, m) 5.17 (1 H, s) 7.29 (1 H, dd, J=8.3, 2.2 Hz) 7.44 (1 H, d, J=2.2 Hz) 7559 (1 H, d, J=8.3 Hz) 8.83 (1 H, t, J=4.8 Hz) (Isomer B).

Workup

  1. temperatureAfter cooling to rt
  2. customThe layers were separated
  3. washthe organic layer was washed with water (25 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate/methanol/acetic acid (8:2:0.1) followed by ethyl acetate/methanol/acetic acid (5:5:0.1))
  8. customto afford crude product which
  9. customwas purified by prep-HPLC (Table 2, Method c)

Sources & evidence

ORD record
ord-5f4675f9999f4609baaa82496332375d
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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