Hydrochloric Acid → HCID 86703610, compound

HRID 1849733Notes

Reaction equation

HRID 1849733 reaction equation
[C:1]([C:4]1[C:5]([O:21][CH2:22][C:23]23[CH2:32][CH:27]4[CH2:28][CH:29]([CH2:31][CH:25]([CH2:26]4)[CH2:24]2)[CH2:30]3)=[CH:6][C:7]([F:20])=[C:8]([CH:19]=1)[C:9]([NH:11][S:12]([N:15]1[CH2:18][CH2:17][CH2:16]1)(=[O:14])=[O:13])=[O:10])(=[O:3])[CH3:2].[CH3:33][Mg]Br.Cl>O1CCCC1.C(OCC)(=O)C>[C:23]12([CH2:22][O:21][C:5]3[C:4]([C:1]([OH:3])([CH3:33])[CH3:2])=[CH:19][C:8]([C:9]([NH:11][S:12]([N:15]4[CH2:18][CH2:17][CH2:16]4)(=[O:14])=[O:13])=[O:10])=[C:7]([F:20])[CH:6]=3)[CH2:24][CH:25]3[CH2:26][CH:27]([CH2:28][CH:29]([CH2:31]3)[CH2:30]1)[CH2:32]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 86703611HCID 86703611, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 86703610HCID 86703610, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-acetyl-4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluorobenzamide (0.200 g, 0.43 mmol) in anhydrous tetrahydrofuran (4 mL) was added methylmagnesium bromide (3.0 M solution in diethyl ether, 0.29 mL, 0.86 mmol) at −78° C. After 1 hour at −78° C., additional methylmagnesium bromide (3.0 M solution in diethyl ether, 0.29 mL, 0.86 mmol) was added; the reaction mixture was allowed to warm to ambient temperature, and stirred for 1 hour. After addition of 1 N hydrochloride acid (5 mL) and diluting the mixture with ethyl acetate (100 mL), the organic phase was washed with brine (5 mL) and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave a residue which was purified by reverse-phase preparative HPLC to give the title compound as a colorless solid (0.101 g, 49%): 1H NMR (300 MHz, DMSO-d6) δ 11.63 (br s, 1H), 7.93 (d, J=9.0 Hz, 1H), 6.96 (d, J=13.0 Hz, 1H), 5.25 (s, 1H), 4.04 (t, J=7.6 Hz, 4H), 3.65 (s, 2H), 2.22-2.10 (m, 2H), 2.01 (br s, 3H), 1.79-1.61 (m, 12H), 1.51 (s, 6H); 19F NMR (282 MHz, DMSO-d6) δ −111.6 (s, 1F); MS (ES−) m/z 479.2 (M−1).

Workup

  1. washthe organic phase was washed with brine (5 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationFiltration and concentration of the filtrate in vacuo
  4. customgave a residue which
  5. customwas purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-470f4f584639438e953ce9cd1a6d55ed
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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