4-Aminobenzoic Acid → HCID 136330138, compound

HRID 1879451Notes

Reaction equation

HRID 1879451 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=1.[NH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.[C:25](=[O:28])(O)[O-:26].[Na+].C([Cl:47])(OC[CH:34]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]2[C:35]1=[CH:36][CH:37]=[CH:38][CH:39]=2)=O>Cl.C(=O)(O)[O-]>[Cl-:47].[C:10]([C:9]1[CH:13]=[CH:14][C:6]([N+:5]#[N:15])=[CH:7][CH:8]=1)([OH:12])=[O:11].[C:45]1([O:26][C:25]([NH:15][CH2:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([OH:24])=[C:22]([N:1]=[N:5][C:6]3[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=3)[CH:23]=2)=[O:28])[C:46]2[CH2:34][C:35]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:41]=2[CH:42]=[CH:43][CH:44]=1

Participants

9

Reactant 5

HCID 9784-Aminobenzoic AcidHCID 5610TyramineHCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 23668193Sodium Nitrite

Product 2

HCID 10921201Benzenediazonium, 4-carboxy-, chlorideHCID 136330138HCID 136330138, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 769Bicarbonate IonSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-carboxy-benzenediazonium chloride was prepared in the following way. Solid NaNO2 (345 mg, 5 mmol, 5 eq.) was added to a cooled suspension of 4-aminobenzoic acid (274 mg, 2 mmol, 2 eq.) in 6 M HCl (4 mL). The resulting mixture was stirred at 0° C. and turned into a slightly yellow-brownish solution. After 15 min the diazonium salt solution was slowly added to a solution of tyramine (137 mg, 1 mmol) in aqueous saturated bicarbonate. The pH of the reaction was kept basic by repeated addition of sodium bicarbonate. The mixture was allowed to slowly warm up to room temperature and was stirred overnight. Next, Fmoc-chloride (285 mg, 1.1 mmol, 1.1. eq) was added. After 1 h, the reaction was acidified with concentrated HCl. The formed solids were filtered and the filtrate was extracted with EtOAc, washed with water, dried over MgSO4 and concentrated under reduced pressure. Solids from extraction and filtration were combined and dry-loaded on a silica column, which was eluted with 0-10% MeOH in dichloromethane/acetic acid 99/1, yielding the title product as an orange-red solid (300 mg, 59% yield). The purity was sufficient for routine solid phase chemistry. An aliquot was further purified for analytical analysis. ESI-MS: 508.3 [M+H]+ 1H NMR (500 MHz, dmso-d6): δ 10.88 (s, 1H), 8.10 (d, 2H, J=8.6 Hz), 8.03 (d, 2H, J=8.6 Hz), 7.87 (d, 2H, J=7.6 Hz), 7.64 (d, 2H, J=7.2 Hz), 7.59 (d, 1H, J=1.8 Hz), 7.42-7.37 (m, 3H), 7.31-7.27 (m, 3H), 7.01 (d, 1H, J=8.4 Hz), 4.27 (d, 2H, J=7.1 Hz), 4.19 (t, 1H, J=7.0 Hz), 3.26-3.21 (m, 2H), 2.72 (t, 2H, J=6.8 Hz). HRMS: found [M+H]+ 508.1700. C30H26N3NaO5+ requires 508.1872.

Workup

  1. temperatureto slowly warm up to room temperature
  2. stirringwas stirred overnight
  3. filtrationThe formed solids were filtered
  4. extractionthe filtrate was extracted with EtOAc
  5. washwashed with water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. extractionSolids from extraction and filtration
  9. washwas eluted with 0-10% MeOH in dichloromethane/acetic acid 99/1

Sources & evidence

ORD record
ord-17785679b24341c0a1ec3f45e2190411
Source dataset
uspto-grants-2012_11
Patent number
US08314215B2

Reaction notes

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