Methanol → HCID 86683247, compound

HRID 1852187Notes

Reaction equation

HRID 1852187 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[C:38]4[C:33](=[C:34]([Cl:39])[CH:35]=[CH:36][CH:37]=4)[C:32]([O:40][CH3:41])=[CH:31][N:30]=3)[CH2:27][C@H:21]2[C:20](=[O:42])[NH:19][C@:18]2([C:44]([O:46]CC)=[O:45])[CH2:43][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH:12]([CH3:49])[CH2:11][C@H:10]1[CH3:50])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].CO>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[C:38]4[C:33](=[C:34]([Cl:39])[CH:35]=[CH:36][CH:37]=4)[C:32]([O:40][CH3:41])=[CH:31][N:30]=3)[CH2:27][C@H:21]2[C:20](=[O:42])[NH:19][C@:18]2([C:44]([OH:46])=[O:45])[CH2:43][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH:12]([CH3:49])[CH2:11][C@H:10]1[CH3:50])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 86683248HCID 86683248, compound

Product 1

HCID 86683247HCID 86683247, compound

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of (2R,6S,7R,13aS,14aR,16aS,Z)-ethyl 6-((tert-butoxycarbonyl)amino)-2-((5-chloro-4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (400 mg, 0.56 mmol) in THF/water (1:1) was added LiOH (235 mg, 5.61 mmol) followed by 5 mL of methanol at room temperature. The reaction mixture was stirred at room temperature for overnight. The solvent was removed under reduced pressure and the residue was diluted with water and acidified by aqueous 1.5 N HCl solutions. The aqueous solution was extracted with ethyl acetate. The combined organic layer was washed with water, dried over anhydrous Na2SO4 and concentrated to get desired product (2R,6S,7R,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-2-((5-chloro-4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid as diastereomeric mixture (310 mg, 81%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionThe aqueous solution was extracted with ethyl acetate
  4. washThe combined organic layer was washed with water
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3a34ae8e18aa4f439a9e1e477f671269
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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