Carbodiimide → HCID 16678876, compound

HRID 551156Notes

Reaction equation

HRID 551156 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][C:9]([CH2:19][NH2:20])([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].N=C=N.[Cl:24][C:25]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:26]=1[C:27](O)=[O:28]>ClCCl>[Cl:24][C:25]1[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[CH:30][C:26]=1[C:27]([NH:20][CH2:19][C:9]1([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH2:10][CH2:11][N:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])[CH2:7][CH2:8]1)=[O:28]

Participants

5

Reactant 3

HCID 160435CarbodiimideHCID 111183632-chloro-4-(trifluoromethyl)benzoic AcidHCID 67173190HCID 67173190, compound

Product 1

HCID 16678876HCID 16678876, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a large glass container with a sealable lid was placed 1-[1-(ethylsulfonyl)-4-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]methanamine (11, 350 mg, 1.15 mmol). Dichloromethane (50 ml) and PS-carbodiimide resin (474 mg, 2.299 mmol) were added along with 2-chloro-4(trifluoromethyl)benzoic acid (336 mg, 1.495 mmol). The lid was sealed and the bottle was shaken for 0.5 hours. The resin was filtered off and washed with EtOAc (3×25 ml) and the organics concentrated in vacuo to give an off-white solid. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to give 2-chloro-N-{[1-(ethylsulfonyl)-4-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]methyl}-4-(trifluoromethyl)benzamide (12) as a white solid. Calculated HRMS 511.164 Found 511.1649. 1H NMR (300 MHz D6DMSO): δ 8.51 (s, 1 H)), 7.96 (s, 1 H), 7.80 (d, J=8.1 Hz, 1 H), 7.61 (d, J=7.8 Hz, 1 H), 3.77 (d, J=9.3 Hz, 2 H), 3.41 (s, 2 H), 3.32 (m, 2 H), 3.29 (s, 2H), 3.21 (s, 4 H), 3.45 (q, J=9 Hz, 2 H), 1.66 (m, 1 H), 1.61 (m, 2 H), 1.564 (s, 2 H), 1.47 (m, 2 H), 1.30 (d, J=4.5 Hz, 2 H), 1.21 (t, J=7.5 Hz, 3 H).

Workup

  1. customThe lid was sealed
  2. filtrationThe resin was filtered off
  3. washwashed with EtOAc (3×25 ml)
  4. concentrationthe organics concentrated in vacuo
  5. customto give an off-white solid
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with EtOAc/Hexanes

Sources & evidence

ORD record
ord-9f5cc987c963451ba5b8678951af6a1e
Source dataset
uspto-grants-2011_05
Patent number
US07947714B2

Reaction notes

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