methyl (S)-2-amino-3-(4-butoxy-phenyl)-propionate → tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoate

HRID 1779148Notes

Reaction equation

HRID 1779148 reaction equation
[F:1][C:2]([F:55])([CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]/[C@H:11]([C:25](N1[C@@H](C(C)C)C(C2C=CC=CC=2)(C2C=CC=CC=2)SC1=O)=[O:26])[C@@:12]([OH:24])([CH2:20][CH2:21][O:22][CH3:23])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[NH2:56][C@@H:57]([CH2:62][C:63]1[CH:68]=[CH:67][C:66]([O:69][CH2:70][CH2:71][CH2:72][CH3:73])=[CH:65][CH:64]=1)[C:58]([O:60][CH3:61])=[O:59]>ClCCl>[CH2:70]([O:69][C:66]1[CH:65]=[CH:64][C:63]([CH2:62][C@H:57]([NH:56][C:25]([C@@H:11](/[CH:10]=[CH:9]/[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]([F:1])([F:55])[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[C@@:12]([OH:24])([CH2:20][CH2:21][O:22][CH3:23])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:26])[C:58]([O:60][CH3:61])=[O:59])=[CH:68][CH:67]=1)[CH2:71][CH2:72][CH3:73]

Participants

4

Reactant 2

HCID 68030835methyl (S)-2-amino-3-(4-butoxy-phenyl)-propionateHCID 90060173tert-Butyl (E)-(2S,3S)-12,12-difluoro-2-hydroxy-3-((S)-4-isopropyl-2-oxo-5,5-diphenyl-thiazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-nonadec-4-enoate

Product 1

HCID 90060174tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoateYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl (E)-(2S,3S)-12,12-difluoro-2-hydroxy-3-((S)-4-isopropyl-2-oxo-5,5-diphenyl-thiazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-nonadec-4-enoate (No. 5552816; 17.0 mg, 0.0216 mmol) and methyl (S)-2-amino-3-(4-butoxy-phenyl)-propionate (8.2 mg, 0.0324 mmol) were dissolved in dichloromethane and the solvent was distilled off. The resulting mixture was stirred at 50° C. for 2.5 days, cooled to room temperature, and subsequently the residue was purified by preparative TLC (33% ethyl acetate/n-hexane, Rf=0.6) to obtain tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-butoxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-(2-methoxy-ethyl)-nonadec-4-enoate (No. 5552820; 13.9 mg, 87% yield).

Workup

  1. distillationthe solvent was distilled off
  2. temperaturecooled to room temperature
  3. customsubsequently the residue was purified by preparative TLC (33% ethyl acetate/n-hexane, Rf=0.6)

Sources & evidence

ORD record
ord-b74f59b476524946bfdd67c632187a40
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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