Triethylamine → Tert-butyl 3-[(4R)-4-(3,3-dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-ylcarbamate

HRID 2224916Notes

Reaction equation

HRID 2224916 reaction equation
[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][CH2:4][C@:5]1([CH3:22])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[C:7]([C:16](OCC)=O)[C:6]1=[O:21].[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:28][C:27]=1[S:40]([NH2:43])(=[O:42])=[O:41].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][CH2:4][C@:5]1([CH3:22])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[C:7]([C:16]2[NH:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:38])[CH3:36])=[CH:28][C:27]=3[S:40](=[O:41])(=[O:42])[N:43]=2)[C:6]1=[O:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 54740013Ethyl(4R)-4-(3,3-dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalene-2-carboxylateHCID 59805694HCID 59805694, compound

Product 1

HCID 135869460Tert-butyl 3-[(4R)-4-(3,3-dimethylbutyl)-1-hydroxy-4-methyl-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 49-4 (330.1 g, 0.999 mol) in toluene (1500 mL) was added the product of Example 17A-4 (287.1 g, 0.999 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 (505.4, 4.99 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 (1500 mL) was added. The organic layer was washed with 10% KH2PO4 and 10% NaCl then concentrated to a thick oil then chased with dichloromethane. The crude title compound (assay for 375.8 g, 68%) was used directly in the next step.

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-9b8643c687e24e5a842b95dd77fd15c3
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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