Diisopropylethylamine → (2R)-5-(amino)-2-[(R)-3-benzyloxytetradecanoylamino]-pentan-1-ol benzyloxymethyl ether

HRID 1920602Notes

Reaction equation

HRID 1920602 reaction equation
C(OC([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:18][C:19](=[O:41])[CH2:20][C@H:21]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:16][OH:17])=O)C1C=CC=CC=1.Cl[CH2:43][O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:45]([O:44][CH2:43][O:17][CH2:16][C@H:15]([NH:18][C:19](=[O:41])[CH2:20][C@H:21]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:14][CH2:13][CH2:12][NH2:11])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 137983Benzyl chloromethyl etherHCID 16086982(2R)-5-(Benzyloxycarbonylamino)-2-[(R)-3-benzyloxytetradecanoylamino]pentan-1-ol

Product 1

HCID 16086984(2R)-5-(amino)-2-[(R)-3-benzyloxytetradecanoylamino]-pentan-1-ol benzyloxymethyl etherYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R)-5-(benzyloxycarbonylamino)-2-[(R)-3-benzyloxytetradecanoylamino]pentan-1-ol (Section 1.1.2.) (2.05 g; 3.60 mmol.) in anhydrous CH2Cl2 (40 ml) at room temperature and under argon flow, there are added in succession BOMC1 (benzyl chloromethyl ether) (reagent grade 60%, 1.25 ml; 5.41 mmol; 1.5 eq.) and diisopropylethylamine (942 μl; 5.41 mmol.; 1.5 eq.). The reaction mixture is then stirred overnight at room temperature and evaporated thereafter to dryness. By running a flash chromatography purification on a silica gel (2/1 petroleum ether/EtOAc eluent), there is recovered the O-benzyloxymethyl derivative (2.28 g; 92%) as a white crystalline solid. (Rf=0.70 in 1/3 petroleum ether/EtOAc mixture, phosphomolybdinium acid and UV color developer) m.p.=97-100° C. A solution of this product (2.00 g; 2.90 mmol.) in HPLC-grade EtOH (220 ml) containing Et3N (4 ml) is hydrogenated in presence of 20% Pd(OH)2 on carbon (200 mg) at room temperature and under atmospheric pressure hydrogen for a period of 3 hours. The catalyst is filtered off. The filtrate is evaporated to dryness and the residue is then dried by suction from a vacuum pump to obtain the free amine (1.58 g; 98%) as an amorphous solid. [α]D=1° (c=1.20; CHCl3) 1H-NMR (250 MHz, CDCl3), δ in ppm: 7.45-7.21 (m, 10H, Ar), 6.52 (d, 1H, NH), 4.80-4.45 (m, 6H, 2×CH2-ph, O—CH2—O), 4.10 (m, 1H, H−3′), 3.83 (m, 1H, H−2), 3.62 (dd, 1H, H−1), 3.47 (dd, 1H, H−1), 2.65 (t, 2×H−5), 2.40 (m, 2H, 2×H−2′), 1.80-1.40 (m, 8H, 2×H−4, 2×H−3, 2×H−4′, NH2), 1.40-1.20 (m, 18H, 9×CH2), 0.88 (t, 3H, CH3); 13C-NMR (62.89 MHz, CDCl3), δ in ppm: 170.78; 138.24; 137.63; 128.38; 128.32; 127.66; 127.62; 94.82; 76.70; 71.26; 69.63; 69.44; 48.48; 41.82; 41.47; 33.83; 31.84; 29.88; 29.58; 29.56; 29.51; 29.27; 29.04; 25.11; 22.62; 14.06.

Workup

  1. customevaporated
  2. customa flash chromatography purification on a silica gel (2/1 petroleum ether/EtOAc eluent), there
  3. customis recovered the O-benzyloxymethyl derivative (2.28 g; 92%) as a white crystalline solid
  4. additionA solution of this product (2.00 g; 2.90 mmol.) in HPLC-grade EtOH (220 ml) containing Et3N (4 ml)
  5. waitis hydrogenated in presence of 20% Pd(OH)2 on carbon (200 mg) at room temperature and under atmospheric pressure hydrogen for a period of 3 hours
  6. filtrationThe catalyst is filtered off
  7. customThe filtrate is evaporated to dryness
  8. customthe residue is then dried by suction from a vacuum pump

Sources & evidence

ORD record
ord-5f31df79a8774d3cb8ea69d16a1b68c8
Source dataset
uspto-grants-2012_05
Patent number
US08173133B2

Reaction notes

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