Trimethylolethane → HCID 71607797, compound

HRID 1424845Notes

Reaction equation

HRID 1424845 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27](=[O:30])[NH:28][CH3:29])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[B:36]([OH:38])[OH:37].[OH:39][CH2:40][C:41]([CH2:45]O)([CH2:43]O)[CH3:42].CC(C)([O-])C.[K+:52].C1COCC1>C1COCC1>[K+:52].[Cl:1][C:2]1[CH:7]=[C:6]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27](=[O:30])[NH:28][CH3:29])=[C:18]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[B-:36]12[O:39][CH2:40][C:41]([CH3:45])([CH2:43][O:37]1)[CH2:42][O:38]2

Participants

5

Reactant 3

HCID 6502TrimethylolethaneHCID 66863523KOtBu THFHCID 71263621HCID 71263621, compound

Product 1

HCID 71607797HCID 71607797, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (2-chloro-4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenyl)boronic acid (0.0750 g, 0.135 mmol) and 1,1,1-tris(hydroxymethyl)ethane (0.0180 g, 0.148 mmol) in anhydrous THF (6 mL) was added activated 3 angstrom molecular sieves (0.400 g). The resulting mixture was heated to reflux for 4 hours and cooled to RT. The mixture was filtered to remove solids and the filtrate concentrated to dryness at reduced pressure. The residue was dissolved in 5 mL of anhydrous THF and the solution cooled to 0° C. The solution was treated with 1M potassium t-butoxide/THF (135 μL, 0.135 mmol) by dropwise addition. After warming to RT the solution was concentrated to dryness at reduced pressure to afford the title compound as a light yellow solid in quantitative yield. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (d, J=4.0 Hz, 1H) 8.09 (s, 1H) 7.98 (dd, J=8.9, 5.5 Hz, 2H) 7.51 (d, J=7.9 Hz, 1H) 7.39 (t, J=8.9 Hz, 2H) 7.07-7.18 (m, 3H) 3.55 (s, 6H) 3.28 (s, 3H) 2.82 (d, J=3.4 Hz, 3H) 2.10-2.23 (m, 1H) 0.73-1.04 (m, 4H) 0.45 (s, 3H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 4 hours
  3. filtrationThe mixture was filtered
  4. customto remove solids
  5. concentrationthe filtrate concentrated to dryness at reduced pressure
  6. dissolutionThe residue was dissolved in 5 mL of anhydrous THF
  7. temperaturethe solution cooled to 0° C
  8. temperatureAfter warming to RT the solution
  9. concentrationwas concentrated to dryness at reduced pressure

Sources & evidence

ORD record
ord-13f3aaf390424dafaf930f27785f798f
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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