Dichloromethane → HCID 11713898, compound

HRID 269473Notes

Reaction equation

HRID 269473 reaction equation
C(O[N:6]([CH2:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]4[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=4[F:43])=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)[CH:15]=1)=[O:12])[C:7](C)=O)(C)(C)C.FC(F)(F)C(O)=O.C(Cl)[Cl:52]>Cl>[ClH:52].[ClH:52].[CH3:7][NH:6][CH2:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH:21]2[CH2:22][CH2:23][N:24]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][C:35]4[CH:40]=[C:39]([F:41])[C:38]([F:42])=[CH:37][C:36]=4[F:43])=[CH:32][CH:33]=3)[CH2:25][CH2:26]2)[CH:15]=1)=[O:12]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86604270HCID 86604270, compound

Product 1

HCID 11713898HCID 11713898, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

2-[(tert-butoxy)-N-methylcarbonylamino]-N-[4-methyl-3-(1-{[4-(2,4,5-trifluorophenoxy) phenyl]methyl}(4-piperidyl))phenyl]acetamide was dissolved in CH2Cl2 (15 mL) and trifluoroacetic acid (5 mL) was added dropwise to the stirred solution. Stirring was continued for 30 minutes then the reaction mixture was concentrated in vacuo to give a gum. This was partitioned between CH2Cl2 (2×30 mL) and saturated aqueous NaHCO3 (30 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo to give the free base. This was dissolved in methanolic hydrogen chloride (1.6 M, 5 mL), and concentrated in vacuo to yield 2-(methylamino)-N-[4-methyl-3-(1-{[4-(2,4,5-trifluorophenoxy)phenyl]methyl}(4-piperidyl))phenyl]acetamide dihydrochloride (292 mg, 88% yield) as a white solid. LCMS (method A): 7.35 min, 498.3 (M+H)+; 1H NMR (D6-DMSO) δ 11.20 (br s, 1H), 10.68 (s, 1H), 9.03 (m, 2H), 7.84 (td, J=10.7, 7.7 Hz, 1H), 7.67 (m, 2H), 7.59 (dt, J=11.0, 8.0 Hz, 1H), 7.40 (m, 2H), 7.13 (d, J=8.5 Hz, 1H), 7.09 (m, 2H), 4.27 (d, J=5.1 Hz, 2H), 3.90 (t, J=5.7 Hz, 2H), 3.39 (d, J=11.8 Hz, 2H), 3.06 (m, 2H), 2.95 (m, 1H), 2.61 (t, J=5.4 Hz, 3H), 2.26 (s, 3H), 2.04 (m, 2H,), 1.86 (d, J=13.4 Hz, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customto give a gum
  3. customThis was partitioned between CH2Cl2 (2×30 mL) and saturated aqueous NaHCO3 (30 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give the free base
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce0d9341ce734a069579798122f175d9
Source dataset
uspto-grants-2008_11
Patent number
US07446204B2

Reaction notes

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