Acetic Acid → HCID 86722465, compound

HRID 718852Notes

Reaction equation

HRID 718852 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20](=[O:22])[CH2:21][C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[N:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH:39]=O.C(O)(=O)C>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[N:15]=[C:14]4[CH2:17][CH2:18][CH2:19][C:20](=[O:22])/[C:21](=[CH:39]/[C:34]5[CH:35]=[CH:36][CH:37]=[CH:38][N:33]=5)/[C:13]4=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 142732-PyridinecarboxaldehydeHCID 2733832Lithium HexamethyldisilazideHCID 86722466HCID 86722466, compound

Product 1

HCID 86722465HCID 86722465, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

1-(4-Fluorophenyl)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6 (1H)-one (114, R1=4-Fluorophenyl) (15.0 g, 50.8 mmol) and THF (430 mL) were stirred until a solution formed. The mixture was cooled to about −70° C. then LiHMDS (1M in THF, 53 mL, 53.0 mmol) was added keeping the internal temperature between about −65 and −70° C. After about 45 min picolinaldehyde (16.32 g, 152 mmol) was added. After about 5 min the mixture was allowed to warm to about −10° C. over about 90 min. Acetic acid (5.8 mL, 102 mmol) was added to the mixture then the slurry was concentrated under reduced pressure. The material was partitioned between water (500 mL), sat. aq. NaHCO3 (˜75 mL) and DCM (200 mL). The aqueous layer was extracted with DCM (60 mL) then the combined organics were dried over MgSO4, filtered and concentrated on the rotovap to yield (E)-1-(4-fluorophenyl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[b]pyrazolo[4,3-e]pyridin-6(1H)-one which was used directly in the next step without further manipulation; LC/MS, method 3, Rt=2.46 min, MS m/z 385 (M+H)+.

Workup

  1. customformed
  2. customthe internal temperature between about −65 and −70° C
  3. temperatureto warm to about −10° C. over about 90 min
  4. concentrationthe slurry was concentrated under reduced pressure
  5. customThe material was partitioned between water (500 mL), sat. aq. NaHCO3 (˜75 mL) and DCM (200 mL)
  6. extractionThe aqueous layer was extracted with DCM (60 mL)
  7. dry with materialthe combined organics were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated on the rotovap

Sources & evidence

ORD record
ord-d987c1f5c3fc4f899cad236f1277c672
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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