Trimethyl borate → tert-butyl N-[4-[3-[2-(hydroxymethyl)-6-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 723183Notes

Reaction equation

HRID 723183 reaction equation
C([Li])CCC.I[C:7]1[C:12]([CH3:13])=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:14][OH:15].B(OC)(OC)OC.C(=O)([O-])[O-].[Na+].[Na+].[C:29]([O:33][C:34](=[O:55])[NH:35][C:36]([C:38]1[S:39][C:40]([S:53][CH3:54])=[C:41]([S:43]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48](Br)[CH:47]=2)(=[O:45])=[O:44])[CH:42]=1)=[NH:37])([CH3:32])([CH3:31])[CH3:30]>CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[C:29]([O:33][C:34](=[O:55])[NH:35][C:36]([C:38]1[S:39][C:40]([S:53][CH3:54])=[C:41]([S:43]([C:46]2[CH:47]=[C:48]([C:7]3[C:12]([CH3:13])=[CH:11][CH:10]=[CH:9][C:8]=3[CH2:14][OH:15])[CH:49]=[CH:50][CH:51]=2)(=[O:45])=[O:44])[CH:42]=1)=[NH:37])([CH3:32])([CH3:31])[CH3:30]

Participants

9

Reactant 5

HCID 8470Trimethyl borateHCID 10340Sodium CarbonateHCID 15717698(2-Iodo-3-methylphenyl)methanolHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateHCID 178418339Butyllithium

Product 1

HCID 145857676tert-butyl N-[4-[3-[2-(hydroxymethyl)-6-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateYield 74.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

n-Butyllithium (2.5M) [4.03 mL] was added to a solution of (2-iodo-3-methyl-phenyl)-methanol (1.00 g, 4.04 mL) [example 213, step a] in ether [20 mL] at −78° C. and stirred for 0.5 hours. Trimethyl borate [1.13 mL, 10.1 mmol) was added and the solution was stirred for 2 hours at room temperature, followed by evaporation. The crude residue was dissolved in ethanol/toluene (1/2) [30 mL] and 2M sodium carbonate [16.2 mL] followed by addition of {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (0.49 g, 1.01 mmol) [example 27, step c]. The solution was bubbled with argon and then tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.15 mmol) was added. The reaction was refluxed for 3 hours and then cooled to room temperature. Ethyl acetate was added and the crude reaction was washed with brine, dried over magnesium sulfate and evaporated. Column chromatography (50% EtOAc in hexanes) of the residue yielded the title compound (0.40 g, 74%) as a solid. ESI-MS (m/z): Calcd. for C25H28N2O5S3: 532.12; found: 532.7.

Workup

  1. stirringthe solution was stirred for 2 hours at room temperature
  2. customfollowed by evaporation
  3. dissolutionThe crude residue was dissolved in ethanol/toluene (1/2) [30 mL]
  4. customThe solution was bubbled with argon
  5. temperatureThe reaction was refluxed for 3 hours
  6. customthe crude reaction
  7. washwas washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-39b3c720c1f948f89270046d09ee23af
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

Loading…