Acetic Acid → {2-[4-(4-tert-Butoxycarbonylaminobutyl)phenoxy]ethylamino}acetic acid ethyl ester

HRID 1158240Notes

Reaction equation

HRID 1158240 reaction equation
[C:1]([OH:4])(=[O:3])[CH3:2].[C:5]([O:9][C:10](=[O:26])[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][NH2:25])=[CH:18][CH:17]=1)([CH3:8])([CH3:7])[CH3:6].C([BH3-])#N.[Na+].O1CC[CH2:33][CH2:32]1>O>[CH2:32]([O:3][C:1](=[O:4])[CH2:2][NH:25][CH2:24][CH2:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:10]([O:9][C:5]([CH3:8])([CH3:6])[CH3:7])=[O:26])=[CH:21][CH:20]=1)[CH3:33]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 588097964-[4-(2-Aminoethoxy)phenyl]-butylcarbamic acid tert-butyl ester

Product 1

HCID 58809798{2-[4-(4-tert-Butoxycarbonylaminobutyl)phenoxy]ethylamino}acetic acid ethyl esterYield 38%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Dimethylacetone dicarboxylate (1.43 mL, 9.69 mmol) and glacial acetic acid (0.56 mL, 9.70 mmol) were added sequentially to a solution of {4-[4-(2-aminoethoxy)phenyl]-butylcarbamic acid tert-butyl ester (1) (1.0 g, 3.24 mmol) in tetrahydrofuran (20 mL). The reaction was stirred for 2 hours at ambient temperature, then cooled to −30° C. Sodium cyanoborohydride (0.61 g, 9.70 mmol) was added in three portions and the reaction slowly warmed to room temperature over 12 hours. After this time, the reaction was quenched by the addition of water (5 mL). The volatiles was then removed under vacuum to give an oil. This oil was diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organics were washed with water (3×10 mL) and then brine (3×10 mL), dried over anhydrous sodium sulfate and concentrated to give 2 (0.576 g, 38% yield) as a clear oil: 1H NMR (500 MHz, CDCl3) δ 1.44 (s, 9H), 1.46-1.52 (m, 2H), 1.55-1.64 (m, 2H), 2.56-2.58 (m, 4H), 2.64-2.65 (m, 2H), 2.72-2.79 (m, 2H), 2.88-2.93 (m, 2H), 3.74 (d, 6H), 3.88-3.93 (m, 1H), 4.44-4.49 (m, 2H), 6.40 (br, 1H), 6.85 (d, 2H), 7.09 (d, 2H); m/z (ESI) 467.

Workup

  1. temperaturecooled to −30° C
  2. customthe reaction
  3. temperatureslowly warmed to room temperature over 12 hours
  4. customAfter this time, the reaction was quenched by the addition of water (5 mL)
  5. customThe volatiles was then removed under vacuum
  6. customto give an oil
  7. extractionextracted with ethyl acetate (3×10 mL)
  8. washThe combined organics were washed with water (3×10 mL)
  9. dry with materialbrine (3×10 mL), dried over anhydrous sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f6d3155207aa427fa56934328e2f23d9
Source dataset
uspto-grants-2010_10
Patent number
US07807834B2

Reaction notes

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