Triethylamine → Tert-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

HRID 494559Notes

Reaction equation

HRID 494559 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](OCC)=O.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:27][C:26]=1[S:39]([NH2:42])(=[O:41])=[O:40].C(N(CC)CC)C>C1(C)C=CC=CC=1>[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]([CH3:15])[CH3:16])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:37])[CH3:35])=[CH:27][C:26]=2[S:39](=[O:40])(=[O:41])[N:42]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 54740012Ethyl(4R)-1-hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalene-2-carboxylateHCID 59805694HCID 59805694, compound

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the product of Example 39-4 (320 g, 1.01 mol) in toluene (1100 mL) was added product of Example 17A-4 (291 g, 1.01 mol). The solution was heated to 100° C. for 4 h then cooled to RT. The solution was transferred to a pressure bottle and triethylamine (472, 4.66 mol) was added and the solution was heated to 100° C. for 26 h. The solution was concentrated to ⅓ of the original volume and ethyl acetate (2000 mL) was added. The organic layer was washed with 10% KH2PO4 and 10% NaCl then concentrated to a thick oil then chased with CH2Cl2. The crude product of Example 39-5 (assay for 406.5 g, 74.5%) was used directly.

Workup

  1. temperaturethen cooled to RT
  2. additionwas added
  3. temperaturethe solution was heated to 100° C. for 26 h
  4. concentrationThe solution was concentrated
  5. additionwas added
  6. washThe organic layer was washed with 10% KH2PO4 and 10% NaCl
  7. concentrationthen concentrated to a thick oil

Sources & evidence

ORD record
ord-8bcf8b6418f94f6598c2c602e2ff0dfc
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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