1-Butanol → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-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]acetate

HRID 1482142Notes

Reaction equation

Br[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[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)[CH2:11][CH2:10]4.C(O)CCC.COC1C=CC=C(OC)C=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:7]1[C:6]([CH3:49])=[C:5]([Cl:50])[C:4]2=[N:32][C:31]3=[CH:2][N:3]2[C:8]=1[N:9]1[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]2[CH:21]=[CH:22][C:23]([F:34])=[CH:24][C:25]=2[C:26]2[CH:33]=[C:30]3[CH:29]=[CH:28][CH:27]=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)-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 (45 mg, 0.058 mmol, 1 equiv), 1-butanol (17.30 mg, 0.233 mmol, 4 equiv) were mixed in DMF (1.1 mL) and water (0.11 mL). To this solution was added Pd(OAc)2 (13.10 mg, 0.058 mmol, 1.0 equiv), Sphos (48 mg, 0.12 mmol, 2 equiv) and cesium carbonate (28.5 mg, 0.088 mmol, 1.5 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 (25 mg, 61.9%) as a brown oil. LCMS (ESI, M+1): 692.3

Workup

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

Sources & evidence

ORD record: ord-88ceec423c9f4a8082d7b02d37ba9338
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409922B2

Reaction notes

Loading…