Acetic Acid → 4-((S)-2-(((S)-3-(3-carboxybenzyl)thiazolidine-2-carbonyl)oxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 2284835Notes

Reaction equation

HRID 2284835 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].[CH:36]([C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[C:41]([OH:43])=[O:42])=O.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(Cl)Cl>[C:41]([C:40]1[CH:39]=[C:38]([CH:46]=[CH:45][CH:44]=1)[CH2:36][N:18]1[CH2:17][CH2:16][S:15][C@H:14]1[C:12]([O:11][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)[CH2:9][C:8]1[C:7]([Cl:34])=[CH:6][N+:5]([O-:35])=[CH:4][C:3]=1[Cl:2])=[O:13])([OH:43])=[O:42]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 120773-Carboxybenzaldehyde2×HCID 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 1181143034-((S)-2-(((S)-3-(3-carboxybenzyl)thiazolidine-2-carbonyl)oxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 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, 570 mg, 1.0 mmol) in DCM (5 mL) was added 3-formylbenzoic acid (180 mg, 1.2 mmol) followed by glacial AcOH (0.17 mL, 3.3 mmol). The reaction was stirred at room temperature for 18 h. Sodium triacetoxyborohydride (690 mg, 3.12 mmol) was added and the reaction was stirred at room temperature for 1.5 h. Additional 3-formylbenzoic acid (180 mg, 1.2 mmol) was added and the reaction mixture was stirred at room temperature for 2 days. DCM (25 mL) and 1 N HCl (15 mL) were added to quench the reaction and the mixture was 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 1.5 h
  2. stirringthe reaction mixture was stirred at room temperature for 2 days
  3. customto quench
  4. customthe reaction
  5. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-59249ddd702f447792d02dc99dfd60c2
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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