Acetic Acid → HCID 59432380, compound

HRID 507144Notes

Reaction equation

HRID 507144 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]([F:52])([F:51])[C:17]1[CH:18]=[C:19]([CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1)[CH2:20][N:21]([C:38]1[N:39]=[N:40][N:41]([CH3:43])[N:42]=1)[C@H:22]1[CH2:28][CH2:27][CH2:26][NH:25][C:24]2[CH:29]=[C:30]([C:34]([F:37])([F:36])[F:35])[C:31]([CH3:33])=[CH:32][C:23]1=2.[O:53]1[CH2:58][CH2:57][C:56](=O)[CH2:55][CH2:54]1.C(O)(=O)C>C(#N)C.ClCCl>[F:52][C:16]([F:51])([F:15])[C:17]1[CH:18]=[C:19]([CH:44]=[C:45]([C:47]([F:50])([F:48])[F:49])[CH:46]=1)[CH2:20][N:21]([C@H:22]1[CH2:28][CH2:27][CH2:26][N:25]([CH:56]2[CH2:57][CH2:58][O:53][CH2:54][CH2:55]2)[C:24]2[CH:29]=[C:30]([C:34]([F:35])([F:36])[F:37])[C:31]([CH3:33])=[CH:32][C:23]1=2)[C:38]1[N:39]=[N:40][N:41]([CH3:43])[N:42]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 59432408(S)-(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine

Product 1

HCID 59432380HCID 59432380, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Add sodium triacetoxyborohydride (0.153 g, 0.724 mmol) portionwise to a solution of (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine (Example 3, Step 18) (0.100 g, 0.181 mmol), tetrahydro-4-pyranone (0.054 g, 0.543 mmol) and glacial acetic acid (1 mL) in acetonitrile (10 mL) at room temperature under an atmosphere of nitrogen and stir for 24 h. Quench the reaction with saturated sodium bicarbonate (5 mL) and dilute with dichloromethane (15 mL). Separate the layers and wash the organic layer with saturated sodium bicarbonate and brine (20 mL each). Dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (80:20), to provide the title compound as an off-white solid (0.070 g, 61%). 1H NMR (CDCl3, 300 MHz) δ 0.87-0.95 (m, 1H), 1.24-1.34 (m, 1H), 1.61-2.10 (m, 6 H), 2.30 (s, 3H), 2.75-2.90 (m, 1H), 3.15-3.22 (m, 1H), 3.41-3.62 (m, 3H), 3.96-4.10 (m, 2H), 4.14 (s, 3H), 4.75-4.95 (m, 2H), 5.37-5.50 (m, 1H), 6.96 (s, 1H), 7.20 (s, 1H), 7.30 (s, 1H), 7.65 (s, 1H), 7.72 (s, 1H); ESI MS m/z 637 [C28H29F9N6O+H]+.

Workup

  1. customQuench
  2. customthe reaction with saturated sodium bicarbonate (5 mL)
  3. customSeparate the layers
  4. washwash the organic layer with saturated sodium bicarbonate and brine (20 mL each)
  5. dry with materialDry the organic layer over sodium sulfate
  6. filtrationfilter
  7. customremove the solvent under reduced pressure
  8. customPurify the residue
  9. washeluting with hexanes/ethyl acetate (80:20)

Sources & evidence

ORD record
ord-6c406f8017194f4d91bd1011390a0244
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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