HCID 86681611, compound → HCID 89511876, compound

HRID 571189Notes

Reaction equation

HRID 571189 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]([O:21][C@H:22]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH:40]([F:42])[F:41])=[C:35]([O:43][CH2:44][CH:45]3[CH2:47][CH2:46]3)[CH:34]=1)[CH2:23][C:24]1[C:29]([Cl:30])=[CH:28][N+:27]([O-:31])=[CH:26][C:25]=1[Cl:32])=[O:20])[CH:13]=[CH:12]2)C1C=CC=CC=1>[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[Cl:32][C:25]1[CH:26]=[N+:27]([O-:31])[CH:28]=[C:29]([Cl:30])[C:24]=1[CH2:23][C@@H:22]([C:33]1[CH:38]=[CH:37][C:36]([O:39][CH:40]([F:42])[F:41])=[C:35]([O:43][CH2:44][CH:45]2[CH2:47][CH2:46]2)[CH:34]=1)[O:21][C:19](=[O:20])[CH2:18][N:14]1[C:15]2[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=2)[CH:12]=[CH:13]1

Participants

3

Reactant 1

HCID 86681611HCID 86681611, compound

Product 1

HCID 89511876HCID 89511876, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 16218511Pd barium sulfateCatalyst

Procedure

A mixture of (S)-4-(2-(2-(5-(benzyloxy)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (155 mg, 0.227 mmol) and 5% Pd/BaSO4 dry powder (type D1863 Chimet spa) (290 mg, 0.136 mmol) in 20 ml of EtOH was hydrogenated for 5 hours at 50 psi. The catalyst was filtered off, solvent was evaporated and the crude was purified by flash chromatography on silica gel (DCM/MeOH from 99.5:0.5 to 99:1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-hydroxy-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (41.8 mg, 0.070 mmol, 31% yield). MS/ESI+ 593.18 [MH]+, [αD]=+30.50, c=0.6 in DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.67 (s, 1H) 8.54 (s, 2H) 7.12-7.19 (m, 2H) 6.99 (d, 1H) 6.93 (d, 1H) 6.91 (dd, 1H) 6.85 (d, 1H) 7.05 (t, 1H) 6.61 (dd, 1H) 6.24 (dd, 1H) 6.01 (dd, 1H) 5.13 (d, 1H) 4.94 (d, 1H) 3.84 (d, 2H) 3.42 (dd, 1H) 3.20 (dd, 1H) 1.11-1.31 (m, 1H) 0.51-0.66 (m, 2H) 0.27-0.44 (m, 2H)

Workup

  1. dry with materialdry powder (type D1863 Chimet spa) (290 mg, 0.136 mmol) in 20 ml of EtOH
  2. filtrationThe catalyst was filtered off
  3. customsolvent was evaporated
  4. customthe crude was purified by flash chromatography on silica gel (DCM/MeOH from 99.5:0.5 to 99:1)

Sources & evidence

ORD record
ord-6ddb945e733347d5a58252705f62e0cd
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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