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

HRID 1681069Notes

Reaction equation

HRID 1681069 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 ester

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-f6d67eba276d4919b5a6026c0e8819e6
Source dataset
uspto-grants-1992_12
Patent number
US05168103

Reaction notes

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