Iodoform → HCID 86701255, compound

HRID 2276058Notes

Reaction equation

HRID 2276058 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:17][O:16][C:15](=[O:18])[C@H:14]([CH2:19]C(O)=O)[C@@H:13]([O:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[C@H:12]([CH3:29])[O:11][C:10]1=[O:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.SC1C=CC=C[N+]=1[O-].C(N(CC)CC)C.C(I)(I)[I:62]>C1COCC1.[Al].[Hg].O>[C:24]([O:23][C@@H:13]1[C@@H:14]([CH2:19][I:62])[C:15](=[O:18])[O:16][CH2:17][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:10](=[O:30])[O:11][C@H:12]1[CH3:29])(=[O:28])[CH:25]([CH3:27])[CH3:26]

Participants

11

Reactant 6

HCID 6374IodoformHCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 86701256HCID 86701256, compoundHCID 178526253HCID 178526253, compound

Product 1

HCID 86701255HCID 86701255, compoundYield 51%

Reagents, catalysts & solvents 4

HCID 23931MercuryCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 5359268AluminumSolvent

Procedure

To a solution of 2-((3S,7R,8R,9S)-3-(tert-butoxycarbonylamino)-8-(isobutyryloxy)-9-methyl-2,6-dioxo-1,5-dioxonan-7-yl)acetic acid (9.90 g, 23 mmol) in THF (100 mL) was added N-methylmorpholine (2.5 mL, 23 mmol) followed by isobutylchloroformate (3.0 mL, 23 mmol) at 0° C. After stirring for 10 min, a solution of 2-mercaptopyridine N-oxide (3.5 g, 27.5 mmol) and triethylamine (TEA; 3.8 mL, 27.5 mmol) in THF (50 mL) was added slowly and the reaction stirred at 0° C. for 1.5 h in the dark (wrapped flask in aluminum foil). The precipitated N-methylmorpholine-HCl salt was removed by vacuum filtration and the filtrate was removed in vacuo at ambient temperature (about 22° C.). The oily residue was dissolved in CH2Cl2 (250 mL) and treated with Iodoform (11.8 g, 30 mmol). The solution was transferred to a UV reactor and irradiated with a 450 W mercury lamp with water cooling. After 1 h, the orange solution was removed from the reactor, adsorbed to Celite® and partially purified via flash chromatography (SiO2, 20% EtOAc/DCM). Additional flash chormatography (SiO2, 10% EtOAc/DCM) followed by recrystallization from EtOAc/hexanes afforded the title compound (5.99 g, 51%) as an off-white solid: mp 168-171° C.; IR (neat) 3386, 2977, 1771, 1760, 1742, 1689, 1510 cm−1; 1H NMR (400 MHz, CDCl3) δ 5.36 (s, 1H), 5.21 (m, 1H), 5.00 (t, J=9.7 Hz, 1H), 4.86 (m, 2H), 3.68 (brs, 1H), 3.31 (dd, J=11.5, 9.3 Hz, 1H), 3.02 (m, 2H), 2.63 (m, 1H), 1.45 (s, 9H), 1.27 (d, J=6.3 Hz, 3H), 1.22 (d, J=7.0 Hz, 6H); ESIMS m/z 536.3 ([M+Na]+).

Workup

  1. customThe precipitated N-methylmorpholine-HCl salt was removed by vacuum filtration
  2. customthe filtrate was removed in vacuo at ambient temperature (about 22° C.)
  3. dissolutionThe oily residue was dissolved in CH2Cl2 (250 mL)
  4. customThe solution was transferred to a UV reactor
  5. waitAfter 1 h
  6. customthe orange solution was removed from the reactor
  7. custompartially purified via flash chromatography (SiO2, 20% EtOAc/DCM)
  8. customAdditional flash chormatography (SiO2, 10% EtOAc/DCM) followed by recrystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-af95898a8d8d431ea665a33d54f15652
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

Loading…