Dichloromethane → HCID 57526924, compound

HRID 1452673Notes

Reaction equation

HRID 1452673 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]([OH:16])=O)=[CH:8][CH:7]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[C:36]([NH2:41])[CH:35]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].Cl.CN(C)CCCN=C=NCC.C(Cl)Cl>CN(C)C1C=CN=CC=1.CN(C=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][C:14]([NH:41][C:36]2[CH:35]=[C:34]([CH:31]3[CH2:30][CH2:29][N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH2:33][CH2:32]3)[CH:39]=[CH:38][C:37]=2[F:40])=[O:16])=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57526931HCID 57526931, compoundHCID 57526939HCID 57526939, compound

Product 1

HCID 57526924HCID 57526924, compoundYield 25.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 25-mL RB-flask was charged with 3-[4-(3,4-difluorophenoxy)phenyl]propanoic acid (180 mg, 0.650 mmol), tert-butyl-4-(3-amino-4-fluorophenyl)-1-piperidine carboxylate (180 mg, 0.610 mmol), 1-[3-(Dimethylamino) propyl]-3-ethylcarbodimide hydrochloride (1.22 mmol, 190 mg), 4-dimethylaminopyridine (20 mg) in DMF:DCM (0.4:4.0 mL) at room temperature. The reaction mixture was stirred for 12 h and water (10.0 mL) was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with CHCl3 (3×10 mL) The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by chromatography (silica gel, hexanes:EtOAc 6:1) to afford tert-butyl 4-[3-({3-[4-(3,4-difluorophenoxy)phenyl]propanoyl}amino)-4-fluorophenyl]-1-piperidinecarboxylate (85.0 mg, 25.0%): 1H NMR (400 MHz, CDCl3) δ 8.32-8.15 (m, 1H), 7.47-6.45 (m, 10H), 4.41-4.07 (br, 2H), 3.17-2.96 (m, 2H), 2.90-2.67 (m, 4H), 2.67-2.56 (m, 1H), 1.91-1.69 (m, 2H), 1.68-1.48 (m, 2H), 1.47 (s, 9H); ESMS m/e 553.3 (M−H+).

Workup

  1. customat room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CHCl3 (3×10 mL) The combined organic extracts
  4. washwere washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by chromatography (silica gel, hexanes:EtOAc 6:1)

Sources & evidence

ORD record
ord-886d4f6da4d843b7b94e483a85650611
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

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