Methyl iodide → HCID 86618126, compound

HRID 2242321Notes

Reaction equation

HRID 2242321 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:31][CH2:32][S:33][CH3:34])[C:13]([NH:15][C@H:16]1[CH2:25][CH2:24][C:19]2([O:23][CH2:22][CH2:21][O:20]2)[CH2:18][C@H:17]1[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:35][I:36]>>[I-:36].[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:13](=[O:14])[NH:15][C@H:16]1[CH2:25][CH2:24][C:19]2([O:20][CH2:21][CH2:22][O:23]2)[CH2:18][C@H:17]1[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:31][CH2:32][S+:33]([CH3:35])[CH3:34])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 6328Methyl iodideHCID 57978119HCID 57978119, compound

Product 1

HCID 86618126HCID 86618126, compound

Procedure

Example 1, Alternative Step 9b: Methionine amide 2 (75.0 g, 0.15M) was dissolved in MeI (225 mL, 3 mL/g)—some off gassing was noted but no exotherm. The reaction mass was left to stir in the dark for 16.5 h. After this time a thick light yellow precipitate had formed. The flask was then evacuated to 200 mmHg and some of the MeI removed. The remaining material was slurried in TBMF (500 mL), after a 30 min stir-out the slurry was filtered, the cake washed with TBMF (500 mL). NMR analysis of this material indicated a small amount of MeI remaining. The cake was re-slurried in TBMF (500 mL), filtered, washed with TBMF (500 mL) and dried under vacuum to give [(3S)-3-benzyloxycarbonylamino-3-{(7R,8S)-7-ethoxycarbonyl-1,4-di-oxa-spiro[4.5]dec-8-ylcarbamoyl}-propyl]-dimethylsulfonium iodide 3 as a free flowing off-white solid (93.5 g, 97%, 99 area % purity). 1H-NMR: (300 MHz, CDCl3) δ 7.75 (d, J 9.0 Hz, 1H), 7.38-7.27 (m, 5H), 6.40 (d, J 7.0 Hz, 1H), 5.10 (s, 2H), 4.76-4.65 (m, 1H), 4.48-4.39 (m, 1H), 4.14-3.85 (m, 6H), 3.84-7.73 (m, 1H), 3.68-3.55 (m, 1H), 3.21 (s, 3H), 3.12 (s, 3H), 2.90-2.83 (s, 1H), 2.52-1.55 (m, 8H), 1.24 (t, J 7.0 Hz, 3H). HPLC: YMC-Pack Pro C18 5 μm 4.6×150 mm, 0.05% TFA (20% MeOH, 80% H2O), to 0.05% TFA (20% MeOH, 80% MeCN), 0-100% 10 min gradient. 2.45 min (I−), 8.14 min (Compound 3, 43.6 AP, I−54.6 AP). HRMS: m/z 509.2341 [Calc: C25H37N2O7S 509.2321].

Workup

  1. waitThe reaction mass was left
  2. customAfter this time a thick light yellow precipitate had formed
  3. customThe flask was then evacuated to 200 mmHg
  4. customsome of the MeI removed
  5. waitThe remaining material was slurried in TBMF (500 mL), after a 30 min
  6. stirringstir-out the slurry
  7. filtrationwas filtered
  8. washthe cake washed with TBMF (500 mL)
  9. filtrationfiltered
  10. washwashed with TBMF (500 mL)
  11. customdried under vacuum

Sources & evidence

ORD record
ord-4929ee1c47cf40cc8d42e02bd7bd5b59
Source dataset
uspto-grants-2010_03
Patent number
US07671062B2

Reaction notes

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