Dichloromethane → HCID 66700208, compound

HRID 1717211Notes

Reaction equation

HRID 1717211 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:11]=[C:12]([C@H:16]2[CH2:20][CH2:19][C@:18]3([CH2:24][CH2:23][NH:22][C:21]3=[O:25])[N:17]2C(OC(C)(C)C)=O)[CH:13]=[CH:14][CH:15]=1.C(O)(C(F)(F)F)=O.[Cl:40]CCl>>[ClH:40].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:11]=[C:12]([C@H:16]2[CH2:20][CH2:19][C@:18]3([CH2:24][CH2:23][NH:22][C:21]3=[O:25])[NH:17]2)[CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59468914HCID 59468914, compound

Product 1

HCID 66700208HCID 66700208, compound

Procedure

To a solution of 1,1-dimethylethyl (2R,5R)-2-(3-{[(2-fluorophenyl)methyl]oxy}phenyl)-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate (D46, 200 mg, 0.45 mmol) in dichloromethane (2 mL) cooled at 0° C., was added TFA (0.4 mL) dropwise and the ice-bath removed. After 1 h the solvent was evaporated under vacuum and the crude mixture purified by SCX column to give the title compound as the free base (154 mg, quant.); Rt (HPLC) 3.58 min. The free base (77 mg, 0.23 mmol) was dissolved in dichloromethane (2.5 mL), and o the resulting solution cooled at 0° C. HCl (0.29 mL of a 1M solution in diethyl ether, 0.29 mmol) was added dropwise. After 15 min the solvent was removed under reduced pressure and the resulting solid triturated with diethyl ether to give the title compound (68 mg, 80%); Rt (HPLC) 3.72 min. MS: (ES/+) m/z: 341 [MH+]; C20H21FN2O2 requires 340; 1H NMR (500 MHz, DMSO-d6) δ (ppm): 10.13 (br. s., 1H), 8.94 (br. s., 1H), 8.39-8.53 (m, 1H); 7.57 (t, 1H), 7.41-7.47 (m, 1H); 7.38 (t, 1H), 7.31-7.35 (m, 1H); 7.22-7.30 (m, 2H); 7.17 (d, 1H), 7.10 (d, 1H), 5.13-5.18 (m, 2H); 4.72 (br. s, 1H), 3.34-3.41 (m, 2H); 2.25-2.68 (m, 5H), 2.12 (br. s, 1H).

Workup

  1. customthe ice-bath removed
  2. customAfter 1 h the solvent was evaporated under vacuum
  3. customthe crude mixture purified by SCX column

Sources & evidence

ORD record
ord-b6acf41e5eb3427db220c7f6f9f1cc30
Source dataset
uspto-grants-2010_09
Patent number
US07803833B2

Reaction notes

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