3-Hydroxybenzaldehyde → 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(((S)-3-(3-hydroxybenzyl)thiazolidine-2-carbonyl)oxy)ethyl)pyridine 1-oxide

HRID 2284836Notes

Reaction equation

HRID 2284836 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[N+:5]([O-:35])[CH:6]=[C:7]([Cl:34])[C:8]=1[CH2:9][C@@H:10]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH:26]([F:28])[F:27])=[C:21]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)[CH:20]=1)[O:11][C:12]([C@H:14]1[NH:18][CH2:17][CH2:16][S:15]1)=[O:13].[OH:36][C:37]1[CH:38]=[C:39]([CH:42]=[CH:43][CH:44]=1)[CH:40]=O.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(Cl)Cl>[Cl:2][C:3]1[CH:4]=[N+:5]([O-:35])[CH:6]=[C:7]([Cl:34])[C:8]=1[CH2:9][C@@H:10]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH:26]([F:28])[F:27])=[C:21]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)[CH:20]=1)[O:11][C:12]([C@H:14]1[N:18]([CH2:40][C:39]2[CH:42]=[CH:43][CH:44]=[C:37]([OH:36])[CH:38]=2)[CH2:17][CH2:16][S:15]1)=[O:13]

Participants

7

Reactant 5

HCID 1013-HydroxybenzaldehydeHCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 710925203,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide hydrochloride

Product 1

HCID 1181142133,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(((S)-3-(3-hydroxybenzyl)thiazolidine-2-carbonyl)oxy)ethyl)pyridine 1-oxide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide hydrochloride (I5, 300 mg, 0.52 mmol) in DCM (2 mL) was added 3-hydroxybenzaldehyde (172 mg, 1.2 mmol) followed by glacial AcOH (0.11 mL, 2.08 mmol). The reaction was stirred at room temperature for 18 hours. Sodium triacetoxyborohydride (500 mg, 2.26 mmol) was added and the reaction was stirred at room temperature for 4 h. DCM (50 mL) and 1 N HCl (20 mL) were added to quench the reaction. The layers were separated and the organic layer washed with 1 N HCl (2×20 mL), passed through a hydrophobic fit and the solvent was removed in vacuo to give the title compound.

Workup

  1. stirringthe reaction was stirred at room temperature for 4 h
  2. customto quench
  3. customthe reaction
  4. customThe layers were separated
  5. washthe organic layer washed with 1 N HCl (2×20 mL)
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-768fe9cbc31e418299a7e3f045dc1fd9
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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