p-Toluenesulfonic acid → HCID 46841134, compound

HRID 1846318Notes

Reaction equation

HRID 1846318 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:9][CH:8]=1)=[O:5].C(C1C=CC(N)=CC=1)(C)(C)C.[Si]([O:39][CH2:40][CH2:41][O:42][C:43]1[C:50]([CH3:51])=[CH:49][C:46]([CH:47]=O)=[CH:45][C:44]=1[CH3:52])(C(C)(C)C)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CC(N(C)C)=O>[C:13]([C:10]1[CH:11]=[CH:12][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:1]=[C:47]2[C:46]2[CH:49]=[C:50]([CH3:51])[C:43]([O:42][CH2:41][CH2:40][OH:39])=[C:44]([CH3:52])[CH:45]=2)=[CH:8][CH:9]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 698614-Tert-ButylanilineHCID 3351772-amino-N-(4-tert-butylphenyl)benzamide2×HCID 23665763Sodium BisulfiteHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 46841134HCID 46841134, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

Following the method described for in Example 21, compound 2-amino-N-(4-tert-butylphenyl)benzamide was made from 4-tert-butylaniline, in 99% yield, and was isolated as a brown solid. 2-Amino-N-(4-tert-butylphenyl)benzamide (1.14 g, 4.25 mmol) and 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde (1.31 g, 4.25 mmol) were combined in DMA (20 mL) and p-TsOH (0.164 g, 0.86 mmol) was added, followed by NaHSO3 (0.488 g, 4.69 mmol). The mixture was heated to 140° C. for 24 hours, before concentrating, diluting with ethyl acetate (250 mL), washing with water (200 mL), and then brine (200 mL), before drying over Na2SO4, filtering, and concentrating. Purification by flash chromatography on silica gel, eluting with 1:1 ethyl acetate/hexanes to 100% ethyl acetate to 10% methanol/ethyl acetate, afforded the title compound as a white solid. 1H-NMR (300 MHz, DMSO-d6) δ 8.19 (d, J=7.2 Hz, 1H), 7.87-7.92 (m, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.56-7.61 (m, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.5 Hz, 2H), 6.96 (s, 2H), 4.83 (t, J=5.4 Hz, 1H), 3.62-3.67 (m, 4H), 2.06 (s, 6H), 1.25 (s, 9H). MS (APCI) m/z: 443 (M+H)+.

Workup

  1. customwas isolated as a brown solid
  2. concentrationbefore concentrating
  3. additiondiluting with ethyl acetate (250 mL)
  4. washwashing with water (200 mL)
  5. dry with materialbrine (200 mL), before drying over Na2SO4
  6. filtrationfiltering
  7. concentrationconcentrating
  8. customPurification by flash chromatography on silica gel
  9. washeluting with 1:1 ethyl acetate/hexanes to 100% ethyl acetate to 10% methanol/ethyl acetate

Sources & evidence

ORD record
ord-dc3449e4cf474a869b3b9ccd4f77c7ee
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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