Diisopropylethylamine → [4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(3-methanesulfonyl-phenyl)-methanone acetate

HRID 1060804Notes

Reaction equation

HRID 1060804 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:8][CH2:7]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[CH3:46][S:47]([C:50]1[CH:51]=[C:52]([CH:56]=[CH:57][CH:58]=1)[C:53]([OH:55])=[O:54])(=[O:49])=[O:48].C(N(CC)C(C)C)(C)C.C([O-])(O)=O.[Na+]>C1COCC1.C(OCC)(=O)C>[C:53]([OH:55])(=[O:54])[CH3:52].[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:7][CH2:8][N:9]([CH:12]2[CH2:13][CH2:14][N:15]([C:53]([C:52]3[CH:56]=[CH:57][CH:58]=[C:50]([S:47]([CH3:46])(=[O:49])=[O:48])[CH:51]=3)=[O:54])[CH2:16][CH2:17]2)[CH2:10][CH2:11]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2203803-Methanesulfonylbenzoic acidHCID 516892Sodium BicarbonateHCID 2733179PyBroPHCID 223974344-(3,4-Dichloro-phenoxy)-[1,4']bipiperidine

Product 1

HCID 22397435[4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(3-methanesulfonyl-phenyl)-methanone acetateYield 73.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Step b (0.15 g) was dissolved in THF (4 ml), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PYBROP™; 0.235 g), 3-methylsulphonylbenzoic acid (0.091 g) and N,N-di-iso-propylethylamine (0.238 ml) were added. After 18 hours at room temperature ethyl acetate and aqueous NaHCO3 solution were added. The product was extracted with ethyl acetate, the combined organic extracts dried with Na2SO4 and concentrated. Purification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAcaq (0.1%) to 95% MeCN//NH4OAcaq (0.1%)) gave the title compound (0.095 g).

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. dry with materialthe combined organic extracts dried with Na2SO4
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAcaq (0.1%) to 95% MeCN//NH4OAcaq (0.1%))

Sources & evidence

ORD record
ord-5444b2f23f074b858538786132a5c9ff
Source dataset
uspto-grants-2003_02
Patent number
US06525070B2

Reaction notes

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