Cesium carbonate → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-5-ethenyl-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]acetate

HRID 1482077Notes

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(C)([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C@H:15]([CH3:35])[O:16][C:17]4[CH:18]=[CH:19][C:20]([F:34])=[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].[B-](F)(F)(F)[CH:51]=[CH2:52].[K+].CO[C:59]1C=CC=C(OC)[C:64]=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.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]([CH:59]=[CH2:64])[C:31]2=[N:32][C:28]3=[CH:29][N:30]2[C:5]=1[N:6]1[CH2:7][CH2:8][C:51]([CH3:52])([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C@H:15]([CH3:35])[O:16][C:17]2[CH:18]=[CH:19][C:20]([F:34])=[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])([CH3:48])([CH3:46])[CH3:47]

Participants

Conditions

Temperature: 80 °C

Procedure

Methyl(2S)-2-[(22S)-5-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 (40 mg, 0.054 mmol, 1.0 equiv), potassium trifluoro(vinyl)borate (36.4 mg, 0.271 mmol, 5 equiv) were mixed in DMF (1.0 mL) and water (0.10 mL). To this solution was added Pd(OAc)2 (1.21 mg, 0.005 mmol, 0.1 equiv), Sphos (4.46 mg, 0.011 mmol, 0.2 equiv) and cesium carbonate (35.4 mg, 0.11 mmol, 2.0 equiv). The solution was degassed by N2 for five minutes. Then it was stirred at 80° C. for 2 hours. The mixture was loaded onto 12 g ISCO column and purified by 0-100% Ethyl Acetate [2% TEA]/Hexane to provide the product (35 mg, 94.3%) as a brown oil. LCMS (ESI, M+1): 684.4.

Workup

customThe solution was degassed by N2 for five minutes
custompurified by 0-100% Ethyl Acetate [2% TEA]/Hexane

Sources & evidence

ORD record: ord-6a39cd0627a949f0983efb79b7d0796d
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409922B2

Reaction notes

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