Acetyl chloride → HCID 66700386, compound

HRID 1690126Notes

Reaction equation

HRID 1690126 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][N:22]([CH3:25])[C:21]3=[O:26])[N:17]2C(OC(C)(C)C)=O)[CH:13]=[CH:14][CH:15]=1.C([Cl:37])(C)=O>C(OCC)(=O)C.CO>[ClH:37].[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][N:22]([CH3:25])[C:21]3=[O:26])[NH:17]2)[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 59468940HCID 59468940, compound

Product 1

HCID 66700386HCID 66700386, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,1-dimethylethyl (2R,5R)-2-(3-{[(2-fluorophenyl)methyl]oxy}phenyl)-7-methyl-6-oxo-1,7-diazaspiro[4.4]nonane-1-carboxylate (D47, 60 mg, 0.13 mmol) in a mixture of ethyl acetate (1 mL) and methanol (0.2 mL) was added AcCl (58 μl, 0.82 mmol) at 0° C. The mixture was stirred for 1 hour at room temperature, solvent removal afforded the title compound. Despite a clean HPLC trace, the product did not become solid. The oil obtained was then submitted to a further purification by SCX column. The free base coming from the SCX (40 mg, 0.11 mmol) was dissolved in dichloromethane (1 mL) and to this solution cooled at 0° C. HCl (0.15 mL of a 1M solution in diethyl ether, 0.15 mmol) was added. After 15 min the solvent was removed under reduced pressure and the solid obtained triturated with diethyl ether. The title compound was obtained as a white solid (40 mg, 80%); Rt (HPLC) 3.72 min; MS: (ES/+) m/z: 355 [MH+]; C21H23FN2O2 requires 354; 1H NMR (500 MHz, DMSO-d6) δ(ppm): 10.62 (br. s., 1H), 9.00 (br. s., 1H), 7.59 (dt, 1H); 7.42-7.48 (m, 1H); 7.39 (t, 1H), 7.34-7.37 (m, 1H); 7.22-7.31 (m, 2H); 7.18 (d, 1H), 7.11 (dd, 1H); 5.11-5.24 (m, 2H), 4.70-4.80 (m, 1H); 3.35-3.45 (m, 2H); 2.78-2.86 (m, 3H); 2.50-2.56 (m, 2H); 2.24-2.46 (m, 3H); 2.00-2.18 (m, 1H).

Workup

  1. customsolvent removal

Sources & evidence

ORD record
ord-c9159aa228f8410fad5441ed7390397a
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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