Propylphosphonic anhydride → HCID 73505388, compound

HRID 1508299Notes

Reaction equation

HRID 1508299 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:11]2([C:28]([F:31])([F:30])[F:29])[CH2:15][C:14]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C:21]3([CH2:27][NH:26][CH2:25]3)[O:20][CH2:19]4)=[N:13][CH2:12]2)[CH:6]=[C:7]([Cl:10])[C:8]=1[F:9].[CH3:32][S:33]([CH2:36][C:37](O)=[O:38])(=[O:35])=[O:34].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[Cl:10][C:7]1[CH:6]=[C:5]([C:11]2([C:28]([F:30])([F:29])[F:31])[CH2:15][C:14]([C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C:21]3([CH2:25][N:26]([C:37](=[O:38])[CH2:36][S:33]([CH3:32])(=[O:35])=[O:34])[CH2:27]3)[O:20][CH2:19]4)=[N:13][CH2:12]2)[CH:4]=[C:3]([Cl:2])[C:8]=1[F:9]

Participants

5

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 37328412-Methanesulfonylacetic acidHCID 90000850HCID 90000850, compound

Product 1

HCID 73505388HCID 73505388, compoundYield 35.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5′-(3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran]hydrochloride (Preparation 9, 0.43 g, 0.87mmol) in THF (10 mL) was added TEA (1.20 mL, 8.67 mmol). Methane sulfonyl acetic acid (0.239 g, 1.74mmol) and T3P (2.74 mL, 4.34mmol) were added at room temperature. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete conversion of starting material, reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (3×10 mL). Combined organic layer was washed with brine (30 mL), dried over sodium sulfate and concentrated to get brown semi solid (0.46 g, crude). Crude compound was purified by column chromatography using Combiflash (redisep column, 12 g). Desired compound was eluted in 60% ethyl acetate in n-hexane to get off white solid (0.23 g. Impure). About 0.23 g was re-purified by preparative TLC to afford white solid (0.18 g). Compound was triturated with chloroform and n-Hexane and washed with distilled n-Hexane to get white solid (0.13 g, 25.9%). 1H NMR (400 MHz, CDCl3) δ: 3.19 (s, 3H), 3.43 (d, J=17.44 Hz, 1H), 3.78 (d, J=17.44 Hz, 1H), 3.86 (s, 2H), 4.34-4.46 (m, 3H), 4.64-4.69 (m, 2H), 4.87 (d, J=16.96 Hz, 1H), 5.16 (s, 2H), 7.32 (d, J=5.88 Hz, 2H), 7.58 (d, J=7.92 Hz, 1H), 7.77 (s, 1H), 7.83 (d, J=7.96 Hz, 1H), LC-MS (m/z): 576.9 (M−H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete conversion of starting material, reaction mixture
  4. customwas quenched with water (10 mL)
  5. extractionextracted with ethyl acetate (3×10 mL)
  6. washCombined organic layer was washed with brine (30 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto get brown semi solid (0.46 g, crude)
  10. customCrude compound was purified by column chromatography
  11. washDesired compound was eluted in 60% ethyl acetate in n-hexane
  12. customto get off white solid (0.23 g. Impure)
  13. customAbout 0.23 g was re-purified by preparative TLC

Sources & evidence

ORD record
ord-6f0cee33eaf34a428475e24f72ce5379
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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