Sodium hydride → Ethyl 4'-{4-[isopropyl-(2,2,2-trifluoroacetyl)amino]butoxy}-3'-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylate

HRID 253482Notes

Reaction equation

HRID 253482 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:12][CH:11]=2)=[CH:6][C:5]=1[C:21]1[CH:30]=[CH:29][C:28]2[C:27]([CH3:32])([CH3:31])[CH2:26][CH2:25][C:24]([CH3:34])([CH3:33])[C:23]=2[CH:22]=1.Br[CH2:36][CH2:37][CH2:38][CH2:39][N:40]([CH:47]([CH3:49])[CH3:48])[C:41](=[O:46])[C:42]([F:45])([F:44])[F:43].[Cl-].[NH4+]>CN(C=O)C>[CH:47]([N:40]([C:41](=[O:46])[C:42]([F:44])([F:45])[F:43])[CH2:39][CH2:38][CH2:37][CH2:36][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][CH:15]=2)=[CH:6][C:5]=1[C:21]1[CH:30]=[CH:29][C:28]2[C:27]([CH3:32])([CH3:31])[CH2:26][CH2:25][C:24]([CH3:33])([CH3:34])[C:23]=2[CH:22]=1)([CH3:48])[CH3:49]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57552328Ethyl 4'-hydroxy-3'-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylateHCID 86053285N-(4-Bromobutyl)-2,2,2-trifluoro-N-isopropylacetamide

Product 1

HCID 86610172Ethyl 4'-{4-[isopropyl-(2,2,2-trifluoroacetyl)amino]butoxy}-3'-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

1.6 g (39 mmol) of 60% sodium hydride are suspended in 200 ml of anhydrous DMF under an inert atmosphere, and the mixture is cooled to 0° C. 13.9 g (32 mmol) of ethyl 4′-hydroxy-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylate dissolved in 20 ml of DMF are added slowly. After 20 minutes, 11.3 g (39 mmol) of N-(4-bromobutyl)-2,2,2-trifluoro-N-isopropylacetamide are added. The reaction medium is then heated at 60° C. for 3 hours, and then cooled to room temperature and poured into 500 ml of saturated ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with water and dried, and the residue obtained is purified by chromatography on a column of silica (eluent: 9/1 heptane/ethyl acetate). A pasty white oil is obtained (m=21.2 g, yield=100%).

Workup

  1. additionare added slowly
  2. temperatureThe reaction medium is then heated at 60° C. for 3 hours
  3. temperaturecooled to room temperature
  4. extractionextracted with ethyl acetate
  5. washThe organic phase is washed with water
  6. customdried
  7. customthe residue obtained
  8. customis purified by chromatography on a column of silica (eluent: 9/1 heptane/ethyl acetate)
  9. customA pasty white oil is obtained (m=21.2 g, yield=100%)

Sources & evidence

ORD record
ord-b3fb3d861e504982811b81ef17401764
Source dataset
uspto-grants-2011_01
Patent number
US07872026B2

Reaction notes

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