Ethyl Acetate → Methyl(2S)-2-[(22S)-8-bromo-5-chloro-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2, 4, 6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetate

HRID 1482141Notes

Reaction equation

HRID 1482141 reaction equation
[Br:1][C:2]1[N:3]2[C:8]3[N:9]4[CH2:37][CH2:36][C:12]([CH3:38])([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([CH3:35])[O:19][C:20]5[CH:21]=[CH:22][C:23]([F:34])=[CH:24][C:25]=5[C:26]5[CH:33]=[C:30]([C:31]=1[N:32]=[C:4]2[CH:5]=[C:6]([CH3:49])[C:7]=3[C@H:39]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:40]([O:42][CH3:43])=[O:41])[CH:29]=[CH:28][CH:27]=5)[CH2:11][CH2:10]4.[Cl:50]N1C(=O)CCC1=O.C(OCC)(=O)C>C(#N)C>[Br:1][C:2]1[N:3]2[C:8]3[N:9]4[CH2:10][CH2:11][C:12]([CH3:38])([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([CH3:35])[O:19][C:20]5[CH:21]=[CH:22][C:23]([F:34])=[CH:24][C:25]=5[C:26]5[CH:33]=[C:30]([C:31]=1[N:32]=[C:4]2[C:5]([Cl:50])=[C:6]([CH3:49])[C:7]=3[C@H:39]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:40]([O:42][CH3:43])=[O:41])[CH:29]=[CH:28][CH:27]=5)[CH2:36][CH2:37]4

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 31398ChlorosuccinimideHCID 118316375Methyl(2S)-2-[(22S)-8-bromo-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2, 4, 6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetate

Product 1

HCID 118316376Methyl(2S)-2-[(22S)-8-bromo-5-chloro-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2, 4, 6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetateYield 57.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl(2S)-2-[(22S)-8-bromo-17-fluoro-4,22,28-trimethyl-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]-2-(tert-butoxy)acetate (50 mg, 0.068 mmol, 1.0 equiv) was dissolved in acetonitrile (1357 μl). To this solution was added 1-chloropyrrolidine-2,5-dione (9.06 mg, 0.068 mmol, 1.0 equiv) and stirred for 3 hours. The mixture was diluted by 15 mL Ethyl Acetate, washed by NaHCO3 and brine. The organic layer was dried, concentrated, and purified on ISCO 12 g column (0-100% EtOAc [2% TEA]/Hexane) to give the product (30 mg, 0.039 mmol, 57.3% yield).

Workup

  1. washwashed by NaHCO3 and brine
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. custompurified on ISCO 12 g column (0-100% EtOAc [2% TEA]/Hexane)

Sources & evidence

ORD record
ord-5bb39f65706c4a4aa5f0bb2bf68792c0
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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