Diisopropylethylamine → HCID 73505598, compound

HRID 1508305Notes

Reaction equation

HRID 1508305 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][CH:12]=[C:11]([C:14]3[CH:25]=[CH:24][C:17]4[C:18]5([CH2:23][NH:22][CH2:21]5)[O:19][CH2:20][C:16]=4[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(C(C)C)C(C)C.[CH3:39][S:40]([CH2:43][C:44](O)=[O:45])(=[O:42])=[O:41].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:28])([F:27])[F:29])[O:13][CH:12]=[C:11]([C:14]3[CH:25]=[CH:24][C:17]4[C:18]5([CH2:23][N:22]([C:44](=[O:45])[CH2:43][S:40]([CH3:39])(=[O:42])=[O:41])[CH2:21]5)[O:19][CH2:20][C:16]=4[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 37328412-Methanesulfonylacetic acidHCID 90001238HCID 90001238, compound

Product 1

HCID 73505598HCID 73505598, compoundYield 61.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of hydrochloride salt of 5′-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrofuran-3-yl]-3′H-spiro[azetidine-3,1′-[2]benzofuran](Preparation 16, 0.5 g, 1.04 mmol) in THF (6 mL) was added DIPEA (1.82 mL, 10.45 mmol) at room temperature and stirred for 10 minutes at room temperature. Methane sulfonyl acetic acid (0.289 g, 2.09 mmol) and T3P (50% solution in ethyl acetate, 3.1 mL, 5.22 mmol) were added at room temperature. Resulting reaction mixture was stirred for 16 hours at room temperature under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (25 mL) and extracted with ethyl acetate (5×25 mL). Combined organic layer was washed with saturated solution of NaHCO3 (2×100 mL), dried over sodium sulphate and concentrated in vacuo to get pale yellow oil (0.62 g, crude). Crude was purified by column chromatography using 100-200 mesh silica gel. Desired product gets eluted in 0.7% MeOH in DCM to afford white semisolid (0.36 g), which was triturated with DCM: n-pentane (1:10; 2×5 mL) to afford off white solid (0.295 g, 50.18%). 1H NMR (400 MHz, CDCl3) δ: 3.17 (s, 3H), 3.21 (d, J=8.4 Hz, 1H), 3.31 (d, J=17.32 Hz, 1H), 3.84 (s, 2H), 4.31 (d, J=10.96 Hz, 1H), 4.41 (d, J=11.24 Hz, 1H), 4.58-4.64 (m, 2H), 5.08 (s, 2H), 7.15 (s, 1H), 7.33 (d, J=7.76 Hz, 1H), 7.40-7.43 (m, 2H), 7.51 (d, J=1.12 Hz, 2H). LC-MS (m/z): 559.7 (M−H).

Workup

  1. customResulting
  2. customreaction mixture
  3. stirringwas stirred for 16 hours at room temperature under nitrogen atmosphere
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (25 mL)
  6. extractionextracted with ethyl acetate (5×25 mL)
  7. washCombined organic layer was washed with saturated solution of NaHCO3 (2×100 mL)
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated in vacuo
  10. customto get pale yellow oil (0.62 g, crude)
  11. customCrude was purified by column chromatography
  12. washDesired product gets eluted in 0.7% MeOH in DCM

Sources & evidence

ORD record
ord-4e4a2fc7a23c4e969b0476762b788763
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

Loading…