Pyridine → HCID 59003227, compound

HRID 2353979Notes

Reaction equation

HRID 2353979 reaction equation
C(OC(N1C2C(=CC3OC(F)(F)OC=3C=2)[C@@H](N)CCC1)=O)(C)(C)C.C(O[BH-](O[C:35](=[O:37])[CH3:36])OC(=O)C)(=O)C.[Na+].[C:39]([O:43][C:44]([N:46]1[C:59]2[C:51](=[CH:52][C:53]3[O:54][C:55]([F:61])([F:60])[O:56][C:57]=3[CH:58]=2)[C@@H:50]([NH:62][CH2:63][C:64]2[CH:69]=[C:68]([C:70]([F:73])([F:72])[F:71])[CH:67]=[C:66]([C:74]([F:77])([F:76])[F:75])[CH:65]=2)[CH2:49][CH2:48][CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].N1C=CC=CC=1.C(Cl)(=O)C>ClCCCl.C(Cl)Cl.C(O)(=O)C>[C:39]([O:43][C:44]([N:46]1[C:59]2[C:51](=[CH:52][C:53]3[O:54][C:55]([F:60])([F:61])[O:56][C:57]=3[CH:58]=2)[C@@H:50]([N:62]([C:35](=[O:37])[CH3:36])[CH2:63][C:64]2[CH:65]=[C:66]([C:74]([F:75])([F:77])[F:76])[CH:67]=[C:68]([C:70]([F:72])([F:73])[F:71])[CH:69]=2)[CH2:49][CH2:48][CH2:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

Participants

9

Reactant 5

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 68679502HCID 68679502, compoundHCID 86616085HCID 86616085, compound

Product 1

HCID 59003227HCID 59003227, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-9-Amino-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester (1.8 mmol) in DCE (20 mL), add 3,5-bis(trifluoromethyl)benzylaldehyde (2.8 mmol), acetic acid (cat.), and Sodium triacetoxyborohydride (5.7 mmol). After stirring for 14 h, dilute with DCM (100 mL) and quench with concentrated sodium carbonate (50 mL). Separate the organics, dry over sodium sulfate, and remove solvent under vacuum. Chromatograph using ethyl acetate/hexane (5-25%) to elute. This provides (S)-9-(3,5-Bis-trifluoromethyl-benzylamino)-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester as an oil. MS (ES+): 569 (M+H). To a solution of (S)-9-(3,5-Bis-trifluoromethyl-benzylamino)-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester (0.35 mmol) in DCM (5 mL), add pyridine (1.06 mmol) and acetyl chloride (1.06 mmol). After stirring for 1.5 h remove solvent under vacuum and chromatograph using ethyl acetate/hexane (5-25%) to elute. This provides the title compound as a foam. MS (ES+): 609 (M−H).

Workup

  1. customquench with concentrated sodium carbonate (50 mL)
  2. customSeparate the organics,
  3. dry with materialdry over sodium sulfate
  4. customremove solvent under vacuum
  5. washto elute
  6. stirringAfter stirring for 1.5 h
  7. customremove solvent under vacuum and chromatograph
  8. washto elute

Sources & evidence

ORD record
ord-fa3388c1b1804111a063da93123cce39
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

Loading…