4-Methoxy-2-(trifluoromethyl)phenylboronic acid → tert-butyl(6bR,10aS)-5-[4-methoxy-2-(trifluoromethyl)phenyl]-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate 3,3-dioxide

HRID 51038Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([S:11](=[O:15])(=[O:14])[CH2:12][CH2:13][N:7]3[C@H:6]3[CH2:16][CH2:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][C@@H:5]23)[CH:10]=1.[F:27][C:28]([F:41])([F:40])[C:29]1[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[CH:31][C:30]=1B(O)O>>[CH3:36][O:35][C:33]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[C:4]3[C:8]4=[C:9]([S:11](=[O:15])(=[O:14])[CH2:12][CH2:13][N:7]4[C@H:6]4[CH2:16][CH2:17][N:18]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:19][C@@H:5]34)[CH:10]=2)=[C:29]([C:28]([F:27])([F:40])[F:41])[CH:34]=1

Participants

Reactant 2

HCID 121094604-Methoxy-2-(trifluoromethyl)phenylboronic acid

HCID 21302666tert-butyl(6bR,10aS)-5-bromo-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate 3,3-dioxide

Product 1

HCID 21302663tert-butyl(6bR,10aS)-5-[4-methoxy-2-(trifluoromethyl)phenyl]-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate 3,3-dioxideYield 74.2%

Procedure

The bromo-indoline (0.6 mmol), boronic acid (0.8 mmol) and barium hydroxide (1 mmol) were stirred into a solution of water (4 mL) and DME (8 mL), then heated at 60° C. while bubbling through a stream of Argon gas for 20 min. The reaction mixture was then cooled to room temperature and Pd(PPh3)2Cl2 (0.03 mmol) and PPh3 (0.09 mmol) were quickly added and refluxing resumed for 4 hours. When the reaction was completed as shown by TLC, ethyl acetate (10 mL) was added and the mixture was filtered through a Celite bed. Organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure. This residue was purified on a flash column eluting with 10% EtOAc/Hexanes to give the desired product in 60-95% yield. tert-butyl(6bR,10aS)-5-[4-methoxy-2-(trifluoromethyl)phenyl]-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate 3,3-dioxide (135 mg, 74%) was prepared via coupling of the tert-butyl(6bR,10aS)-5-bromo-1,2,6b,9,10,10a-hexahydropyrido[4,3-b][1,4]thiazino[2,3,4-hi]indole-8(7H)-carboxylate 3,3-dioxide (150 mg, 0.338 mmol) with 2-trifluoromethyl-4-methoxyphenyl boronic acid (112 mg, 0.507 mmol) using the general procedure described above.

Sources & evidence

ORD record: ord-27f88b3fa9fa48fc8b86153facba7148
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06713471B1

Reaction notes

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