Ammonium formate → Methyl(2S)-2-[(22S)-5-bromo-19-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 1482073Notes

Reaction equation

HRID 1482073 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:40]([CH3:41])=[C:39]([Br:42])[C:38]2=[N:43][C:35]3=[C:36](Br)[N:37]2[C:12]=1[N:13]1[CH2:49][CH2:48][C:16]([CH3:50])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:47])[O:23][C:24]2[C:25]([F:46])=[CH:26][CH:27]=[CH:28][C:29]=2[C:30]2[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=2)[CH2:15][CH2:14]1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CN(C=O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:42][C:39]1[C:38]2=[N:43][C:35]3=[CH:36][N:37]2[C:12]([N:13]2[CH2:14][CH2:15][C:16]([CH3:50])([O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@H:22]([CH3:47])[O:23][C:24]4[C:25]([F:46])=[CH:26][CH:27]=[CH:28][C:29]=4[C:30]4[CH:45]=[C:34]3[CH:33]=[CH:32][CH:31]=4)[CH2:48][CH2:49]2)=[C:11]([C@H:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:7]([O:9][CH3:10])=[O:8])[C:40]=1[CH3:41]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 118316318Methyl(2S)-2-(tert-butoxy)-2-[(22S)-5,8-dibromo-19-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]acetate

Product 1

HCID 118316321Methyl(2S)-2-[(22S)-5-bromo-19-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 59.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

Methyl(2S)-2-(tert-butoxy)-2-[(22S)-5,8-dibromo-19-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]acetate (0.13 g, 0.16 mmol, 1.0 equiv) and ammonium formate (0.101 g, 1.6 mmol, 10.0 equiv) were dissolved in DMF (3.19 mL). To this solution was added tetrakis (0.018 g, 0.016 mmol, 0.1 equiv). The mixture was heated at 40° C. overnight. Then it was diluted with ethyl acetate, washed by NaHCO3, dried over MgSO4, concentrated and purified by flash column (24 g, 0-100% EtOAc[2% TEA]/Hex) to afford the product (70 mg, 59.6%). LCMS (ESI, M+1): 736.3.

Workup

  1. washwashed by NaHCO3
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. custompurified by flash column (24 g, 0-100% EtOAc[2% TEA]/Hex)

Sources & evidence

ORD record
ord-de6299c656ee46d2a243b61573ecb8d8
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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