Hydrochloric Acid → (2R,3R)-N-[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanamide, hydrochloride salt

HRID 2282838Notes

Reaction equation

HRID 2282838 reaction equation
[CH:1]1([CH2:8][CH2:9][NH:10][C:11](=[O:29])[C@H:12]([CH3:28])[C@H:13]([C@@H:16]2[CH2:20][CH2:19][CH2:18][N:17]2C(OC(C)(C)C)=O)[O:14][CH3:15])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=[CH:2]1.[ClH:30].O1CCOCC1>>[ClH:30].[CH:1]1([CH2:8][CH2:9][NH:10][C:11](=[O:29])[C@H:12]([CH3:28])[C@@H:13]([O:14][CH3:15])[C@@H:16]2[CH2:20][CH2:19][CH2:18][NH:17]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=[CH:7]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86685734tert-butyl (2S)-2-[(1R,2R)-3-{[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidine-1-carboxylate

Product 1

HCID 131731851(2R,3R)-N-[2-(cyclohepta-2,4,6-trien-1-yl)ethyl]-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanamide, hydrochloride salt

Procedure

Intermediate #63 (400 mg, 0.989 mmol, 1 eq.) was treated with a 4 M solution of hydrochloric acid in dioxane (10 mL, 40 mmol, 40 eq.). After 1 hour, the reaction mixture was concentrated in vacuo and the residue was taken up in dichloromethane and washed with 1 M sodium hydroxide solution. The aqueous layer was back-extracted with dichloromethane and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide #64 (301 mg, quantitative) as a brown oil, which slowly began to solidify upon standing. LC-MS: m/z 305.3 [M+H+], retention time=0.54 minutes; HPLC (Protocol G): retention time=4.848 minutes; 1H NMR (400 MHz, CDCl3), characteristic signals: δ 6.64-6.67 (m, 2H), 6.16-6.22 (m, 2H), 6.08-6.14 (br m, 1H), 5.16-5.22 (m, 2H), 3.44 (s, 3H), 3.31 (dd, J=6.3, 4.5 Hz, 1H), 2.98-3.04 (m, 1H), 2.94 (ddd, J=10.5, 7.2, 5.6 Hz, 1H), 2.81 (ddd, J=10.5, 7.7, 6.7 Hz, 1H), 2.57 (qd, J=7.1, 4.5 Hz, 1H), 1.90-1.97 (m, 2H), 1.49-1.55 (m, 1H), 1.18 (d, J=7.1 Hz, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. washwashed with 1 M sodium hydroxide solution
  3. extractionThe aqueous layer was back-extracted with dichloromethane
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide #64 (301 mg, quantitative) as a brown oil, which

Sources & evidence

ORD record
ord-237cd95444544654936bdfab7d960f9a
Source dataset
uspto-grants-2015_09
Patent number
US09138486B2

Reaction notes

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