Acetic Acid → HCID 86616092, compound

HRID 2353992Notes

Reaction equation

HRID 2353992 reaction equation
C(O[C:6]([N:8]1[C:21]2[C:13](=[CH:14][C:15]3[O:16][C:17]([F:23])([F:22])[O:18][C:19]=3[CH:20]=2)[C@@H:12]([N:24](C(=O)C)[CH2:25][C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=C(C(F)(F)F)[CH:27]=2)[CH2:11][CH2:10][CH2:9]1)=O)(C)(C)C.[F:43][C:44]([F:49])([F:48])[C:45](O)=O.[C:50](O)(=O)[CH3:51].C(O[BH-](O[C:64](=O)[CH3:65])OC(=O)C)(=O)C.[Na+].[CH2:68](Cl)Cl>ClC(Cl)C>[F:43][C:44]([F:49])([F:48])[C:45]1[CH:27]=[C:26]([CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=1)[CH2:25][NH:24][C@@H:12]1[C:13]2=[CH:14][C:15]3[O:16][C:17]([F:23])([F:22])[O:18][C:19]=3[CH:20]=[C:21]2[N:8]([CH2:6][CH:51]2[CH2:50][CH2:65][CH2:64][CH2:68]2)[CH2:9][CH2:10][CH2:11]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6344Dichloromethane3×HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 59003227HCID 59003227, compound

Product 1

HCID 86616092HCID 86616092, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (S)-9-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester (0.26 mmol) in DCM (5 mL) add trifluoroacetic acid (1 mL). After stirring for 1 h, quench the reaction with sodium bicarbonate (5 mL) and dilute with DCM (20 mL). Separate and dry the organics over sodium sulfate. Remove the solvent and chromatograph the product using ethyl acetate/hexane (5-20%) to elute. This provides N-(3,5-Bis-trifluoromethyl-benzyl)-N-(2,2-difluoro-6,7,8,9-tetrahydro-5H-1,3-dioxa-5-aza-cyclohepta[f]inden-9-yl)-acetamide as an oil. To this crude intermediate in DCE (dichloroethane) (5 mL), add cyclopentylcarbaldehyde (1.3 mmol), acetic acid (cat.), and sodium triacetoxyborohydride (1.6 mmol). After stirring for 14 h, dilute the reaction with DCM (20 mL) and quench with concentrated sodium carbonate (5 mL). Separate the organics, dry over sodium sulfate, and remove solvent under vacuum. Chromatograph the product using ethyl acetate/hexane (5-20%) to elute. This provides the title compound as a foam. MS (ES+): 593 (M+H).

Workup

  1. customquench
  2. customthe reaction with sodium bicarbonate (5 mL)
  3. customSeparate
  4. dry with materialdry the organics over sodium sulfate
  5. customRemove the solvent and chromatograph the product
  6. washto elute
  7. stirringAfter stirring for 14 h
  8. additiondilute
  9. customquench with concentrated sodium carbonate (5 mL)
  10. customSeparate the organics,
  11. dry with materialdry over sodium sulfate
  12. customremove solvent under vacuum
  13. washto elute

Sources & evidence

ORD record
ord-d200ab87cecd47a28814dfeec4f80a3d
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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