HCID 22610872, compound → HCID 22610853, compound

HRID 2222065Notes

Reaction equation

HRID 2222065 reaction equation
[N:1]([CH2:4][C:5]([CH2:20][N:21]=[N+]=[N-])([CH3:19])[CH2:6][C:7](=[O:18])[CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[N+]=[N-]>CO.[Pd]>[NH2:21][CH2:20][C:5]([CH2:4][NH2:1])([CH3:19])[CH2:6][C:7](=[O:18])[CH2:8][CH2:9][O:10][Si:11]([C:14]([CH3:16])([CH3:17])[CH3:15])([CH3:12])[CH3:13]

Participants

4

Reactant 1

HCID 22610872HCID 22610872, compound

Product 1

HCID 22610853HCID 22610853, compoundYield 95.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Pd-black (70 mg) was added to a solution of 5 (1 g, 3.05 mmol) in MeOH (27 mL) under N2. The resulting suspension was thoroughly degassed and H2 introduced. After 18 h the suspension was degassed, N2 introduced, filtered through celite (MeOH as eluant) and the solvent removed to give crude 5,5-bis(aminomethyl)-1-O-tert-butyldimethylsilyl-3-oxo-hexan-1-ol (6) (800 mg, 2.90 mmol). This was dissolved in dioxan: 1M aq. NaOH (2:1, 20 mL) and the resulting solution cooled to 0° C. Boc2O (1.4 g, 6.41 mmol) was added and after 30 min. the resulting mixture warmed to RT. After 3 h the reaction mixture was acidified to pH 4 with 1M KHSO4 (aq.) and partitioned between EtOAc (300 mL) and water (100 mL). The aqueous layer was further extracted with EtOAc (200 mL). The organic fractions were combined, washed with sat. NaHCO3 (aq., 100 mL), brine (100 mL), dried (MgSO4), filtered and the solvent removed. The residue was purified by flash chromatography (EtOAc: hexane, 1:9 to 1:3) to give 5,5-bis(aminomethyl)-1-O-tert-butyldimethylsilyl-N,N-di-tert-butoxycarbonyl-3-oxo-hexan-1-ol(7). (1.04 g, 72% over 2 steps) as a colorless oil; IR (film) 3360 (NH), 1701, (amide I), 1508 (amide II) cm−1; 1H NMR (CDCl3, 400 MHz) δ-0.02 (s, 6H, Si(CH3)2), 0.75 (s, 3H, H-6), Q. 81 (s, 9H, SiC(CH3)3), 1.34 (s, 18H, OC(CH3)3×2), 2.83 (dd, 2H, JH,NH 5.3 Hz, JH,H′ 14.0 Hz, —CHH′N—×2), 3.00 (dd, 2H, JH′,NH 7.9 Hz, JH,H′ 14.1 Hz, —CHH′N—×2), 3.16 (s, 2H, H-4), 3.39 (t, 2H, J 4.9 Hz, H-2), 3.65 (t, 2H, J 4.9 Hz, H-1), 5.30 (br t, 2H, J 6.8 Hz, NH×2); 13C NMR (CDCl3, 100 MHz) 8-5.4 (Si(CH3)2), 18.2 (SiC(CH3)), 18.8 (C-6), 25.7 (SiC(CH3)3), 28.3 (OC(CH3)3×2), 40.2 (C-5), 44.4 (—CH2N—), 62.3, 72.8, 76.3 (C-1, C-2, C-4), 78.7 (OC(CH3)3×2), 156.7 (—NH(CO)O—×2); MS m/z (FAB+): 351 (M+Na+, 3), 329 (M+H+, 45).

Workup

  1. customThe resulting suspension was thoroughly degassed
  2. additionH2 introduced
  3. customAfter 18 h the suspension was degassed
  4. additionN2 introduced
  5. filtrationfiltered through celite (MeOH as eluant)
  6. customthe solvent removed

Sources & evidence

ORD record
ord-bb2aec3235fa432db3490c6b23ac0af5
Source dataset
uspto-grants-2008_05
Patent number
US07371553B2

Reaction notes

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