Hydrochloric Acid → (1R)-3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-methyl-1-(3-methylbutyl)naphthalen-2(1H)-one

HRID 2224883Notes

Reaction equation

HRID 2224883 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@@:5]([CH3:17])([CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([NH:29]C(=O)OC(C)(C)C)=[CH:28][C:22]=2[S:21](=[O:38])(=[O:37])[N:20]=1.Cl.O1CCOCC1>ClCCl>[NH2:29][C:27]1[CH:26]=[CH:25][C:23]2[NH:24][C:19]([C:3]3[C:4](=[O:18])[C@:5]([CH3:17])([CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:6]4[C:11]([C:2]=3[OH:1])=[CH:10][CH:9]=[CH:8][CH:7]=4)=[N:20][S:21](=[O:38])(=[O:37])[C:22]=2[CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 135869452Tert-butyl 3-[(4R)-1-hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-ylcarbamate

Product 1

HCID 135869463(1R)-3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-methyl-1-(3-methylbutyl)naphthalen-2(1H)-oneYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Example 39-5 (407 g, 0.754 mol) in dichloromethane (550 mL) was added 4 M HCl in dioxane (760 mL, 3.04 mol) and the solution was mixed at RT for 3.5 h. The reaction was quenched by addition of ethyl acetate (1.5 L) and pH 7 phosphate buffer (1.7 L) and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (400 mL) and the combined organic layers were concentrated and chased with ethanol to a final volume of approximately 2500 mL. The product precipitated and was isolated by filtration and dried to give the title compound (309.7 g, 93.4%).

Workup

  1. additionthe solution was mixed at RT for 3.5 h
  2. customThe reaction was quenched by addition of ethyl acetate (1.5 L) and pH 7 phosphate buffer (1.7 L)
  3. customthe layers were separated
  4. extractionThe aqueous layer was back-extracted with ethyl acetate (400 mL)
  5. concentrationthe combined organic layers were concentrated
  6. customThe product precipitated
  7. customwas isolated by filtration
  8. customdried

Sources & evidence

ORD record
ord-9a3d8579db734144b62ba3aead6553d5
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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