4-Methylmorpholine → Tert-butyl 4-({[(1-aminododecylidene)amino]oxy}carbonyl)benzylcarbamate

HRID 735880Notes

Reaction equation

HRID 735880 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([OH:18])=[O:17])=[CH:12][CH:11]=1)=[O:7])([CH3:4])[CH3:3].CN1CCOCC1.ClC(OCC(C)C)=O.O[NH:35][C:36](=[NH:48])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]>C1COCC1>[NH2:48][C:36](=[N:35][O:17][C:16]([C:13]1[CH:12]=[CH:11][C:10]([CH2:9][NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[CH:15][CH:14]=1)=[O:18])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 178443266N'-hydroxydodecanimidamide

Product 1

HCID 87302441Tert-butyl 4-({[(1-aminododecylidene)amino]oxy}carbonyl)benzylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At 0° C., to a solution of boc-(4-aminomethyl)-benzoic acid (5.000 g, 19.9 mmol), NMM (2.214 g, 21.89 mmol) in anhydrous THF (50 mL) was added dropwise isobutyl chloroformate (2.853 g, 20.89 mmol). The resulting mixture was stirred for 10 min, then N-hydroxydodecanimidamide (Example 23, step a) (6.398 g, 29.85 mmol) was added at once. After 1 h the ice-water bath was removed and the mixture was stirred for 14 h at rt. An aqueous solution of HCl (1N, 50 mL) was added and the mixture was extracted with AcOEt (3×70 mL). The combined organic layers were washed with water (150 mL), dried over MgSO4 and evaporated to give a white solid (9.2 g). This crude product was purified by flash chromatography over silica gel (c-Hex/AcOEt 4/1) to give the title compound as a white solid (7.91 g, 89%). 1H NMR (CDCl3, 300 MHz) δ 7.80 (d, 2H, J=8.0 Hz), 7.50 (t, 1H, J=5.7 Hz) 7.32 (d, 2H, J=8.0 Hz), 6.42 (br s, 1H), 6.27 (br s, 1H), 4.20 (s, 1H), 4.18 (s, 1H), 1.91-2.15 (m, 2H), 1.08-1.66 (m, 27H), 0.86 (t, 3H, J=6.9 Hz). M+(LC/MS(ESI)): 448.4; M−(LC/MS(ESI)): 446.3. HPLC (Condition A), Rt: 5.74 min (HPLC purity: 96.7%).

Workup

  1. customAfter 1 h the ice-water bath was removed
  2. stirringthe mixture was stirred for 14 h at rt
  3. additionAn aqueous solution of HCl (1N, 50 mL) was added
  4. extractionthe mixture was extracted with AcOEt (3×70 mL)
  5. washThe combined organic layers were washed with water (150 mL)
  6. dry with materialdried over MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-a1e6bf445c5b45c58f1a4a32503bbfaf
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

Loading…