Sodium Carbonate → N-Benzyl-N-[5-[3-(methylsulfonyl)-4-(hydroxymethyl)phenyl]thiophene-2-ylmethyl]-2-(trifluoromethyl)benzenesulfonamide

HRID 1665069Notes

Reaction equation

HRID 1665069 reaction equation
[CH2:1]([N:8]([CH2:22][C:23]1[S:24][C:25](Br)=[CH:26][CH:27]=1)[S:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:20])[F:19])(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][S:30]([C:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:35][C:34]=1[CH2:48][OH:49])(=[O:32])=[O:31].[F-].[Cs+].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.COCCOC>[CH2:1]([N:8]([CH2:22][C:23]1[S:24][C:25]([C:37]2[CH:36]=[CH:35][C:34]([CH2:48][OH:49])=[C:33]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:38]=2)=[CH:26][CH:27]=1)[S:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:20])[F:19])(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 25953Cesium fluorideHCID 59251458(2-(Methylsulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanolHCID 67439229N-benzyl-N-(5-bromo-thiophen-2-ylmethyl)-2-trifluoromethyl-benzenesulfonamide

Product 1

HCID 25210583N-Benzyl-N-[5-[3-(methylsulfonyl)-4-(hydroxymethyl)phenyl]thiophene-2-ylmethyl]-2-(trifluoromethyl)benzenesulfonamideYield 39%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of N-benzyl-N-(5-bromo-thiophen-2-ylmethyl)-2-trifluoromethyl-benzenesulfonamide (example 1, step 2, 170 mg), [2-methanesulfonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanol (CAS [918328-16-2], 90 mg), cesium fluoride (88 mg) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium dichloromethane adduct (12 mg) in a 1 M aqueous sodium carbonate solution (0.72 mL) and 1,2-dimethoxyethane (1.5 mL) was heated to 80° C. for 36 h. After cooling to r.t., the mixture was filtered. The filtrate was diluted with ethyl acetate and washed with water. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The product was purified by chromatography (SiO2, cyclohexane/ethyl acetate 1:0 to 0:1) to give N-benzyl-N-[5-(4-hydroxymethyl-3-methanesulfonyl-phenyl)-thiophen-2-ylmethyl]-2-trifluoromethyl-benzenesulfonamide (67 mg) as an off-white solid. MS: 612.6 ([M+NH4]+)

Workup

  1. temperatureAfter cooling to r.t.
  2. filtrationthe mixture was filtered
  3. additionThe filtrate was diluted with ethyl acetate
  4. washwashed with water
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by chromatography (SiO2, cyclohexane/ethyl acetate 1:0 to 0:1)

Sources & evidence

ORD record
ord-0acb9b7649b54d45a106638a39c171ee
Source dataset
uspto-grants-2011_10
Patent number
US08039493B2

Reaction notes

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