Diisopropylethylamine → (S)-1-((S)-1-(4-bromophenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-one

HRID 219613Notes

Reaction equation

HRID 219613 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][CH2:12][CH2:13][CH2:14][C@:15]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([NH2:20])[CH2:16][C:17]([CH3:19])=[CH2:18])[CH3:10])=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.Cl[C:37](Cl)([O:39]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]([N:11]2[CH2:12][CH2:13][CH2:14][C@:15]([CH2:16][C:17]([CH3:19])=[CH2:18])([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:20][C:37]2=[O:39])[CH3:10])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 86639074(S)-N1-((S)-1-(4-bromophenyl)ethyl)-6-methyl-4-phenylhept-6-ene-1,4-diamine HCl salt

Product 1

HCID 59190359(S)-1-((S)-1-(4-bromophenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-oneYield 157.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (S)—N1—((S)-1-(4-bromophenyl)ethyl)-6-methyl-4-phenylhept-6-ene-1,4-diamine HCl salt (0.88 g, 2.2 mmol) in CH2Cl2 (120 mL) was cooled to 0° C. and i-Pr2NEt (1.15 mL, 3 equiv) was added. A solution of triphosgene (215 mg, 0.33 equiv) in CH2Cl2 (15 mL) was added dropwise over 10 min The mixture was stirred for 3 h at 0° C. LC-MS found the reaction completed. The mixture was concentrated, redissolved in 6:1 Ether/EtOAc (70 mL), washed with 1% aq HCl (2×15 mL), satd aq NaHCO3 (10 mL) and brine (10 mL), and dried over over Na2SO4. After filtration and concentration, the residue was purified by chromatography on a 40-g silica gel cartridge, eluted with a 5˜40% EtOAc in Hexanes gradient, to afford (S)-1-((S)-1-(4-bromophenyl)ethyl)-4-(2-methylallyl)-4-phenyl-1,3-diazepan-2-one (487 mg, 52%) as a clear oil. LC-MS Method 1 tR=2.25 min, m/z 427, 429 (M+1); 1H NMR (CDCl3) δ 7.42 (d, 2H), 7.35 (t, 2H), 7.28-7.20 (m, 3H), 6.76 (d, 2H), 5.37 (q, 1H), 5.21 (s, 1h), 4.98 (s, 1H), 4.85 (s, 1H), 2.78 (m, 2H), 2.44 (m, 3H), 1.89 (td, 1H), 1.43 (d, 3H), 1.24 (m, 1H), 1.11 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionredissolved in 6:1 Ether/EtOAc (70 mL)
  3. washwashed with 1% aq HCl (2×15 mL)
  4. dry with materialdried over over Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by chromatography on a 40-g silica gel cartridge
  7. washeluted with a 5˜40% EtOAc in Hexanes gradient

Sources & evidence

ORD record
ord-c7e0623842ac4ce1b9fbd15e5919a3e4
Source dataset
uspto-grants-2012_06
Patent number
US08202857B2

Reaction notes

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