Trifluoroacetic acid → HCID 59432401, compound

HRID 507166Notes

Reaction equation

HRID 507166 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]([F:60])([F:59])[C:10]1[CH:11]=[C:12]([CH:52]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:54]=1)[CH2:13][N:14]([C:46]1[N:47]=[N:48][N:49]([CH3:51])[N:50]=1)[C@H:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH:23]2[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]2)[C:17]2[C:36]([CH3:45])=[C:37]([C:41]([F:44])([F:43])[F:42])[C:38]([CH3:40])=[CH:39][C:16]1=2.C(=O)(O)[O-].[Na+]>ClCCl>[F:58][C:55]([F:56])([F:57])[C:53]1[CH:52]=[C:12]([CH:11]=[C:10]([C:9]([F:8])([F:59])[F:60])[CH:54]=1)[CH2:13][N:14]([C@H:15]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][CH:23]2[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]2)[C:17]2[C:36]([CH3:45])=[C:37]([C:41]([F:42])([F:43])[F:44])[C:38]([CH3:40])=[CH:39][C:16]1=2)[C:46]1[N:47]=[N:48][N:49]([CH3:51])[N:50]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 59432385HCID 59432385, compound

Product 1

HCID 59432401HCID 59432401, compoundYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add trifluoroacetic acid (1.7 mL) slowly to a solution of (S)-tert-butyl 4-{5-[(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)amino]-7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepin-1-ylmethyl}-piperidine-1-carboxylate (Example 159) (0.251 g, 0.329 mmol) in dichloromethane (4 mL) at 0° C. under an atmosphere of nitrogen and stir for 4.5 h. Pour the reaction into saturated sodium bicarbonate (25 mL) and dilute with dichloromethane (15 mL). Separate the layers and extract the aqueous layer with dichloromethane (10 mL). Combine the organic layers, wash with saturated sodium bicarbonate (25 mL), dry over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with dichloromethane/methanol/concentrated ammonium hydroxide (90:10:1), to provide the title compound as a white solid (0.101 g, 46%): 1H NMR (CDCl3, 500 MHz) δ 1.01-1.11 (m, 2H), 1.47-1.66 (m, 3H), 1.73-1.95 (m, 5H), 2.34 (s, 6H), 2.55-2.60 (m, 2H), 2.84-2.87 (m, 2H), 2.98-3.09 (m, 3H), 3.25 (br s, 1H), 4.13 (m, 3H), 4.73-4.96 (m, 1H), 5.12 (br s, 1H), 5.56 (br s, 1H), 6.58 (s, 1H), 7.77 (s, 3H); ESI MS m/z 664 [C30H34F9N7+H]+.

Workup

  1. additionPour
  2. customSeparate the layers
  3. extractionextract the aqueous layer with dichloromethane (10 mL)
  4. washCombine the organic layers, wash with saturated sodium bicarbonate (25 mL)
  5. dry with materialdry over sodium sulfate
  6. filtrationfilter
  7. customremove the solvent under reduced pressure
  8. customPurify the residue
  9. washeluting with dichloromethane/methanol/concentrated ammonium hydroxide (90:10:1)

Sources & evidence

ORD record
ord-bc07678b80814226ac8b1def2911f537
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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