Cesium carbonate → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-19-fluoro-4,5,22,28-tetramethyl-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

HRID 1482075Notes

Reaction equation

HRID 1482075 reaction equation
Br[C:2]1[C:31]2=[N:32][C:28]3=[CH:29][N:30]2[C:5]([N:6]2[CH2:37][CH2:36][C:9]([CH3:38])([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C@H:15]([CH3:35])[O:16][C:17]4[C:18]([F:34])=[CH:19][CH:20]=[CH:21][C:22]=4[C:23]4[CH:33]=[C:27]3[CH:26]=[CH:25][CH:24]=4)[CH2:8][CH2:7]2)=[C:4]([C@H:39]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:40]([O:42][CH3:43])=[O:41])[C:3]=1[CH3:49].[CH3:50]OC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.CB(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:45]([O:44][C@@H:39]([C:4]1[C:3]([CH3:49])=[C:2]([CH3:50])[C:31]2=[N:32][C:28]3=[CH:29][N:30]2[C:5]=1[N:6]1[CH2:7][CH2:8][C:9]([CH3:38])([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C@H:15]([CH3:35])[O:16][C:17]2[C:18]([F:34])=[CH:19][CH:20]=[CH:21][C:22]=2[C:23]2[CH:33]=[C:27]3[CH:26]=[CH:25][CH:24]=2)[CH2:36][CH2:37]1)[C:40]([O:42][CH3:43])=[O:41])([CH3:46])([CH3:47])[CH3:48]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 139377Methylboronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 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)acetate

Product 1

HCID 118316323Methyl(2S)-2-(tert-butoxy)-2-[(22S)-19-fluoro-4,5,22,28-tetramethyl-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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

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 (0.070 g, 0.095 mmol, 1.0 equiv), Pd(OAc)2 (0.013 g, 0.057 mmol, 0.6 equiv), Sphos (0.047 g, 0.114 mmol, 1.2 equiv), methylboronic acid (0.057 g, 0.095 mmol, 10.0 equiv) and cesium carbonate (0.124 g, 0.380 mmol, 4.0 equiv) were mixed in DMF (1.73 mL) and water (0.17 mL). The solution was degassed for five minutes by N2. Then it was stirred at 80° C. for 2 hours. It was diluted by ethyl acetate (15 mL), washed by water, dried over MgSO4 and concentrated to afford the pure enough product for the next reaction. LCMS (ESI, M+1): 658.4.

Workup

  1. customThe solution was degassed for five minutes by N2
  2. additionIt was diluted by ethyl acetate (15 mL)
  3. washwashed by water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto afford the pure enough product
  7. customfor the next reaction

Sources & evidence

ORD record
ord-127f890183334a09b6a970fe8747ab13
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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