Hydrochloric Acid → (+/-)-(E)-ethyl 2-(7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate

HRID 390144Notes

Reaction equation

HRID 390144 reaction equation
O[C:2]([C:4]([F:7])([F:6])[F:5])=O.[Br:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:22]=1[C:16]1([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)[CH2:15][CH:14]2[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O.FC(F)(F)[C:49]1[CH:59]=[CH:58][CH:57]=C[C:50]=1[CH:51]=[CH:52][C:53](O)=[O:54].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>C(Cl)Cl>[Br:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:22]=1[C:16]1([CH2:17][CH2:18][N:19]([C:53](=[O:54])/[CH:52]=[CH:51]/[C:50]3[CH:49]=[CH:59][CH:58]=[CH:57][C:2]=3[C:4]([F:7])([F:6])[F:5])[CH2:20][CH2:21]1)[CH2:15][CH:14]2[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 749393-(2-(Trifluoromethyl)phenyl)-2-propenoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 131730263(+/-)-ethyl 2-(7-bromo-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate TFA salt

Product 1

HCID 44226472(+/-)-(E)-ethyl 2-(7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetateYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (±)-ethyl 2-(7-bromo-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate TFA salt (31 mg, 0.07 mmol) in CH2Cl2 was treated with MP-carbonate resin (2.89 mmol g−1, 200 mg, 0.58 mmol). The mixture was stirred for 0.5 h and filtered. To the filtrate were added ortho-(trifluoromethyl)cinnamic acid (42 mg, 0.19 mmol), i-Pr2NEt (0.07 mL, 0.39 mmol) and solid HATU (37 mg, 0.10 mmol). The mixture was stirred at rt for 4 h. A 10-mL Chem-Elut cartridge was wetted with 5% aq HCl (6 mL) and allowed to stand for 5 min. The reaction mixture was applied and the cartridge was eluted with ether (20 mL). The eluate was passed through a second 10-mL Chem-Elut cartridge that had been prewetted with satd aq NaHCO3 (6 mL). The eluate was evaporated and the residue was purified by preparative HPLC to afford (±)-(E)-ethyl 2-(7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate (15 mg, 42%) as an oil. LC-MS Method 1 tR=2.23, min, m/z=550, 552; 1H NMR (CDCl3) 1.28 (t, 3H), 1.40-1.80 (3H), 2.43 (m, 2H), 2.76 (m, 1H), 2.91 (m, 2H), 3.18 (m, 1H), 3.34 (m, 1H), 3.62 (m, 1H), 4.14 (m, 1H), 4.19 (q, 2H), 4.80 (m, 1H), 6.83 (d, 1H), 7.11 (m, 2H), 7.35-7.75 (5H), 7.92 (m, 1H).

Workup

  1. filtrationfiltered
  2. stirringThe mixture was stirred at rt for 4 h
  3. waitto stand for 5 min
  4. washthe cartridge was eluted with ether (20 mL)
  5. customThe eluate was evaporated
  6. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-4733e7b8f4a74c7b8475a87ef776b5a0
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

Loading…