3-hydroxy-1,2,3-benzotriazin-4(3H)-one → N-(3-(hydroxymethyl)benzyl)succinamic acid tert-butyl ester

HRID 2112432

Reaction equation

HRID 2112432 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH2:14][CH2:15][C:16]([O-:18])=O.ON1C(=O)C2C=CC=CC=2N=N1.[NH2:37][CH2:38][C:39]1[CH:40]=[C:41]([CH2:45][OH:46])[CH:42]=[CH:43][CH:44]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:21]([O:20][C:13](=[O:19])[CH2:14][CH2:15][C:16]([NH:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][OH:46])[CH:40]=1)=[O:18])([CH3:24])([CH3:23])[CH3:22]

Participants

9

Reactant 5

HCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21880609[3-(Aminomethyl)phenyl]methanolHCID 22317022Butanedioic acid,1-(1,1-dimethylethyl) ester

Product 1

HCID 57642058N-(3-(hydroxymethyl)benzyl)succinamic acid tert-butyl esterYield 54%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (451 mg, 2.35 mmol) was added to a solution of mono-tert-butyl succinate (410 mg, 2.35 mmol) and 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazin (384 mg, 2.35 mmol) in a mixture of N,N-dimethylformamide (5 ml) and dichloromethane (5 ml). The reaction mixture was stirred for 25 min at 0° C. A solution of crude (3-(aminomethyl)phenyl)methanol (340 mg, 2.48 mmol) in N,N-dimethylformamide (5 ml) and ethyldiisopropylamine(0.40 ml, 2.48 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. It was diluted with ethyl acetate (150 ml) and washed with a 10% aqueous solution of sodium hydrogensulphate (100 ml). The aqueous phase was extracted with ethyl acetate (50 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (150 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatograpy on silica (60 g), using a mixture of ethyl acetate and heptane (2:1) as eluent to give 372 mg of N-(3-(hydroxymethyl)benzyl)succinamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas slowly warming up to room temperature
  3. washwashed with a 10% aqueous solution of sodium hydrogensulphate (100 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (50 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (150 ml)
  6. dry with materialdried over magnesium sulphate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatograpy on silica (60 g)
  9. additiona mixture of ethyl acetate and heptane (2:1) as eluent

Sources & evidence

ORD record
ord-7f6a68f1125b4e5c8964e40ae0fb4c39
Source dataset
uspto-grants-2009_04
Patent number
US07524813B2

Linked notes

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