Tetrabutylammonium Fluoride → HCID 86722386, compound

HRID 718788Notes

Reaction equation

HRID 718788 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[CH:19]1([NH:22][C:23]([C:25]23[CH2:49][CH2:48][C:47]([O:54][Si](CC)(CC)CC)([C:50]([F:53])([F:52])[F:51])[CH2:46][CH:26]2[CH2:27][CH2:28][CH2:29][C:30]2[C:31]3=[CH:32][C:33]3[CH:34]=[N:35][N:36]([C:39]4[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=4)[C:37]=3[CH:38]=2)=[O:24])[CH2:21][CH2:20]1>C(Cl)Cl>[CH:19]1([NH:22][C:23]([C:25]23[CH2:49][CH2:48][C:47]([OH:54])([C:50]([F:51])([F:53])[F:52])[CH2:46][CH:26]2[CH2:27][CH2:28][CH2:29][C:30]2[C:31]3=[CH:32][C:33]3[CH:34]=[N:35][N:36]([C:39]4[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=4)[C:37]=3[CH:38]=2)=[O:24])[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 86722385HCID 86722385, compound

Product 1

HCID 86722386HCID 86722386, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

TBAF (1 M solution in THF, 0.560 mL, 0.560 mmol) was added to a solution of rac-(3R,4aR,12bS)—N-cyclopropyl-9-(4-fluorophenyl)-3-((triethylsilyl)oxy)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carboxamide (44, R1=4-Fluorophenyl, R2′=Cyclopropyl, R3=Trifluoromethyl) (0.230 g, 0.374 mmol) and DCM (6 mL). After about 1 h, TBAF (1 M solution in THF, 0.30 mL, 0.30 mmol) was added. After about 30 min, DCM (50 mL) was added. The solution was washed with water (4×20 mL) and sat. aq. NaCl (20 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was loaded onto silica gel (6 g) and purified on silica gel (40 g) using a gradient of 0-30% EtOAc in DCM. The product fractions were combined and concentrated to give rac-(3R,4aR,12bS)—N-cyclopropyl-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carboxamide (45, R1=4-Fluorophenyl, R2′=Cyclopropyl, R3=Trifluoromethyl) (0.150 g, 78% yield); LC/MS, method 3, Rt=2.46 min.; MS m/z: 502 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.31 (d, J=0.8 Hz, 1H), 7.88 (s, 1H), 7.84-7.74 (m, 2H), 7.57 (s, 1H), 7.45-7.36 (m, 2H), 6.37 (d, J=3.8 Hz, 1H), 5.89 (s, 1H), 2.90-2.64 (m, 2H), 2.63-2.50 (m, 2H), 2.50-2.36 (m, 2H), 2.17-2.06 (m, 1H), 2.03-1.88 (m, 2H), 1.81-1.66 (m, 2H), 1.58-1.35 (m, 2H), 1.32-1.13 (m, 1H), 0.56-0.40 (m, 2H), 0.37-0.15 (m, 2H).

Workup

  1. waitAfter about 30 min
  2. washThe solution was washed with water (4×20 mL) and sat. aq. NaCl (20 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified on silica gel (40 g)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-489aa7f3cac7469e91bd5fc39aee6f1c
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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