HCID 57546125, compound → HCID 57546196, compound

HRID 913959Notes

Reaction equation

HRID 913959 reaction equation
Br[C:2]1(Br)[C:10]2[C:5](=[C:6]([CH:15]([O:17][CH2:18][C:19]3([C:32]4[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=4)[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)[CH3:16])[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[NH:4][C:3]1=[O:39]>C(O)(=O)C.[Zn]>[F:38][C:35]1[CH:36]=[CH:37][C:32]([C:19]2([CH2:18][O:17][CH:15]([C:6]3[CH:7]=[C:8]([C:11]([F:13])([F:12])[F:14])[CH:9]=[C:10]4[C:5]=3[NH:4][C:3](=[O:39])[CH2:2]4)[CH3:16])[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:21][CH2:20]2)=[CH:33][CH:34]=1

Participants

4

Reactant 1

HCID 57546125HCID 57546125, compound

Product 1

HCID 57546196HCID 57546196, compoundYield 62.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of tert-butyl 4-((1-(3,3-dibromo-2-oxo-5-(trifluoromethyl)indolin-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (27.9 mg, 0.040 mmol) in acetic acid (500 μL) cooled briefly in a cold water bath was added zinc dust <10 micron (18 mg, 0.275 mmol). TLC (30% ethyl acetate/hexanes) after 15 minutes showed complete conversion of starting material. After 45 minutes the mixture was filtered through celite with ethyl acetate and concentrated. The crude material was purified on SiO2 eluting with 30% ethyl acetate/hexanes to give the product (13.3 mg, 0.025 mmol, 62%) as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.55-7.62 (m, 2H), 7.32 (s, 1H), 7.20-7.28 (m, 2H), 7.11 (s, 1H), 7.04 (t, J=8.69 Hz, 2H), 4.28 (q, J=6.55 Hz, 1H), 3.64-3.81 (m, 2H), 3.42 (s, 2H), 3.23-3.36 (m 2H), 2.88-3.08 (m, 2H), 2.16-2.25 (m, 1H), 2.04-2.12 (m, 1H), 1.67-1.85 (m, 1H), 1.57-1.64 (m, 1H), 1.42 (s, 9H), 1.29 (d, J=6.55 Hz, 3H); Mass spec. (M-H)−: 535.6.

Workup

  1. filtrationAfter 45 minutes the mixture was filtered through celite with ethyl acetate
  2. concentrationconcentrated
  3. customThe crude material was purified on SiO2 eluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-785d6e7c2eae4eb8a4891791b17b7fc0
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…