Isobutyric Acid → HCID 123850736, compound

HRID 1508306Notes

Reaction equation

HRID 1508306 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]([C:19]1[CH:24]=[C:23]([Cl:25])[C:22]([Cl:26])=[C:21]([Cl:27])[CH:20]=1)=[CH:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[C:12]1([CH2:18][NH:17][CH2:16]1)[O:11][CH2:10]2)=[O:6].CCN(CC)CC.[C:37](O)(=[O:41])[CH:38]([CH3:40])[CH3:39].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[F:29][C:2]([F:1])([F:28])[C:3]([C:19]1[CH:20]=[C:21]([Cl:27])[C:22]([Cl:26])=[C:23]([Cl:25])[CH:24]=1)=[CH:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[C:12]1([CH2:18][N:17]([C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[CH2:16]1)[O:11][CH2:10]2)=[O:6]

Participants

7

Reactant 5

HCID 6590Isobutyric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90000837HCID 90000837, compound

Product 1

HCID 123850736HCID 123850736, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the stirred solution of hydrochloride salt of 5′-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-2-enoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran](Preparation 26, 1.0 g, 2.2 mmol, 1 eq) in DMF (10 mL) was added Et3N (2.4 mL, 17.3mmol, 8 eq) followed by addition of iso-butyric acid (0.38 g, 4.32mmol, 2 eq), HOBt (0.29 g, 2.16 mmol, 1 eq) and EDC.HCl (0.62 g, 3.24 mmol, 1.5 eq) at room temperature. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After consumption of starting material, reaction mixture was quenched by water (30 mL) and extracted with ethyl acetate (3×25 mL). Combined organic layer was washed with aqueous sodium bicarbonate (50 mL), aqueous LiCl solution (2×50 mL), brine (50 mL) and dried over sodium sulfate. Organic layer was concentrated in vacuo to get brown sticky oil (1.0 g, Crude). Purification was done by Combiflash chromatography using 40 g Redisep column. Compound was eluted in 40% ethyl acetate in n-hexane to get title compound as off white solid (0.5 g, 43%). 1H NMR (400 MHz, CDCl3) δ: 1.13-1.17 (m, 6H), 2.46-2.53 (m, 1H), 4.25 (d, J=10.64 Hz, 1H), 4.30-4.34 (m, 2H), 4.52 (d, J=9.32 Hz, 1H), 5.15 (s, 2H), 7.27 (s, 2H), 7.40 (d, J=1.36 Hz, 1H), 7.49 (d, J=8.04 Hz, 1H), 7.68 (s, 1H), 7.84 (d, J=7.92 Hz, 1H). LC-MS (m/z): 531.9 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter consumption of starting material, reaction mixture
  4. customwas quenched by water (30 mL)
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. washCombined organic layer was washed with aqueous sodium bicarbonate (50 mL), aqueous LiCl solution (2×50 mL), brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationOrganic layer was concentrated in vacuo
  9. customto get brown sticky oil (1.0 g, Crude)
  10. customPurification
  11. washCompound was eluted in 40% ethyl acetate in n-hexane

Sources & evidence

ORD record
ord-9bbeb48d63a24f28977378efec97fa2b
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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