1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → [4-(4-Benzyloxycarbonylaminobutyl)phenoxy]acetic acid 2-tert-butoxycarbonylamino-ethyl ester

HRID 1175722Notes

Reaction equation

HRID 1175722 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:26]=[CH:25][C:19]([O:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:18][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.[C:39]([O:43][C:44](=[O:49])[NH:45][CH2:46][CH2:47]O)([CH3:42])([CH3:41])[CH3:40]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:39]([O:43][C:44]([NH:45][CH2:46][CH2:47][O:23][C:22](=[O:24])[CH2:21][O:20][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])=[CH:26][CH:25]=1)=[O:49])([CH3:42])([CH3:41])[CH3:40]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 22054455[4-(4-{[(Benzyloxy)carbonyl]amino}butyl)phenoxy]acetic acid

Product 1

HCID 67350250[4-(4-Benzyloxycarbonylaminobutyl)phenoxy]acetic acid 2-tert-butoxycarbonylamino-ethyl esterYield 48.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

[4-(4-Benzyloxycarbonylaminobutyl)phenoxy]acetic acid 48 (240 mg, 0.67 mmol) was dissolved in anhydrous CH2Cl2 (6 mL). To the solution was added DMAP (98 mg, 0.80 mmol), followed by EDC-HCl (154 mg, 0.81 mmol). The reaction mixture was stirred at room temperature for 15 min. (2-Hydroxyethyl)carbamic acid tert-butyl ester (0.21 mL, 1.34 mmol) was then added and the stirring was continued for 16 h. Solvent was removed by rotary evaporation. The residue was subjected to flash silica gel column chromatography eluting with ethyl acetate/dichloromethane (1:20, 1:15, and 1:10, v/v) to give the desired ester 44a as a colorless oil (162 mg, 48% yield). 1H NMR (300 MHz, CDCl3) δ 1.35-1.65 (m, 4H), 1.44 (s, 9H), 2.45-2.58 (m, 2H), 3.10-3.22 (m, 2H), 3.25-3.42 (m, 2H), 4.18-4.28 (m, 2H), 4.62 (s, 2H), 4.70 (br s, 1H), 4.84 (br s, 1H), 5.08 (s, 2H), 6.81 (d, 2H), 7.07 (d, 2H), 7.25-7.38 (m, 5H). m/z (ESI) 501 [C27H36N2O7+H]+.

Workup

  1. additionwas then added
  2. customSolvent was removed by rotary evaporation
  3. washeluting with ethyl acetate/dichloromethane (1:20, 1:15, and 1:10

Sources & evidence

ORD record
ord-04170000074b4a559dd3f62d180c616c
Source dataset
uspto-grants-2010_11
Patent number
US07842697B2

Reaction notes

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