tert-butyl (E)-(2S,3S)-11-(2-heptyl-[1,3]dioxolan-2-yl)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-undec-4-enoate → tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(2-hept yl-[1,3]dioxolan-2-yl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

HRID 1779197Notes

Reaction equation

HRID 1779197 reaction equation
[CH2:1]([C:8]1([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]/[CH:19]=[CH:20]/[C@H:21]([C:35](N2[C@@H](C(C)C)C(C3C=CC=CC=3)(C3C=CC=CC=3)OC2=S)=[O:36])[C@@:22]([OH:34])([CH2:30][CH2:31][O:32][CH3:33])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[O:12][CH2:11][CH2:10][O:9]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[NH2:58][C@@H:59]([CH2:64][C:65]1[CH:70]=[CH:69][C:68]([O:71][CH2:72][CH2:73][CH2:74][CH3:75])=[CH:67][CH:66]=1)[C:60]([NH:62][CH3:63])=[O:61]>ClCCl>[CH2:72]([O:71][C:68]1[CH:67]=[CH:66][C:65]([CH2:64][C@H:59]([NH:58][C:35]([C@@H:21](/[CH:20]=[CH:19]/[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:8]2([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[O:9][CH2:10][CH2:11][O:12]2)[C@@:22]([OH:34])([CH2:30][CH2:31][O:32][CH3:33])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:36])[C:60](=[O:61])[NH:62][CH3:63])=[CH:70][CH:69]=1)[CH2:73][CH2:74][CH3:75]

Participants

4

Reactant 2

HCID 90060091tert-butyl (E)-(2S,3S)-11-(2-heptyl-[1,3]dioxolan-2-yl)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-undec-4-enoateHCID 90060342(S)-2-amino-3-(4-butoxy-phenyl)-N-methyl-propionamide

Product 1

HCID 131734861tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(2-hept yl-[1,3]dioxolan-2-yl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoateYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

No. 6801291, tert-butyl (E)-(2S,3S)-11-(2-heptyl-[1,3]dioxolan-2-yl)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-undec-4-enoate (62 mg, 0.0824 mmol) and (S)-2-amino-3-(4-butoxy-phenyl)-N-methyl-propionamide (23 mg, 0.0989 mmol) were dissolved in dichloromethane. The solvent was distilled off under reduced pressure. The resulting residue was reacted at 45° C. for 4 days. After confirming the consumption of the starting materials by LCMS, the reaction mixture was purified with SP1 to obtain No. 6801292, tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methylcarbamoyl-ethylcarbamoyl]-11-(2-hept yl-[1,3]dioxolan-2-yl)-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate (33 mg, 54% yield, ESI (LC/MS positive mode) m/z 762 (M+H); Rt 3.02 min.). To the obtained No. 6801292 (40 mg, 0.0526 mmol) were added dichloromethane (3.0 mL) and trifluoroacetic acid (1.0 mL), and the mixture was stirred at room temperature. After confirming the consumption of the starting materials by LCMS, the solvent was distilled off under reduced pressure. The residue was purified by preparative HPLC. The purified fraction was freeze-dried to obtain the title compound (27 mg, 78% yield, white powder).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customThe resulting residue was reacted at 45° C. for 4 days
  3. customthe consumption of the starting materials by LCMS
  4. customthe reaction mixture was purified with SP1
  5. customto obtain No

Sources & evidence

ORD record
ord-746b45a9c53d498eb57d674b2f6090d4
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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