tert-Butyl bromoacetate → [3-[[(1,1-Dimethylethyloxycarbonyl)methyl]amino]propyl]carbamic acid phenylmethyl ester

HRID 2255478Notes

Reaction equation

HRID 2255478 reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH2:13][NH2:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.Br[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]>CN(C)C=O>[C:1]1([CH2:7][O:8][C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 81531DiisopropylethylamineHCID 417669Benzyl (3-aminopropyl)carbamate

Product 1

HCID 10663622[3-[[(1,1-Dimethylethyloxycarbonyl)methyl]amino]propyl]carbamic acid phenylmethyl esterYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3-aminopropyl)carbamic acid phenylmethyl ester (7.08 g, 34 mmol) and N,N-diisopropylethylamine (4.5 mL, 26 mmol) in anhydrous dimethylformamide (100 mL) under nitrogen was cooled to 10° C. and treated with t-butyl bromoacetate (2.80 mL, 17 mmol) over 5 minutes. After one hour the bath was removed and the reaction mixture was stirred overnight, poured into water (500 mL), and made basic (pH 12) with 2.5N sodium hydroxide solution. The aqueous layer was extracted with dichloromethane (2×250 mL), which was dried over sodium sulfate and concentrated in vacuo with heat to remove dimethylformamide. The residue was purified by flash chromatography (9 cm diameter, gradient elution with 2.5-3.5% methanol in dichloromethane) to yield [3-[[(1,1-dimethylethyloxycarbonyl)methyl]amino]propyl]carbamic acid phenylmethyl ester as a pale yellow oil (4.50 g, 82%); 1H NMR (CDCl3, 200 MHz): δ 7.35 (m, 5H), 5.43 (br s, NH), 5.09 (s, 2H), 3.35-3.24 (m, 4H), 2.68 (t, J=6.5 Hz, 2H), 1.68 (p, J=6.5 Hz, 2H), 1.46 (s, 9H).

Workup

  1. customAfter one hour the bath was removed
  2. additionpoured into water (500 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×250 mL), which
  4. dry with materialwas dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. temperaturewith heat
  7. customto remove dimethylformamide
  8. customThe residue was purified by flash chromatography (9 cm diameter, gradient elution with 2.5-3.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f152d075c8bb4c948edd986ed5459d79
Source dataset
uspto-grants-1993_08
Patent number
US05240946

Reaction notes

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