Phenol → HCID 9923094, compound

HRID 1582457Notes

Reaction equation

HRID 1582457 reaction equation
C([O-])([O-])=O.[K+].[K+].[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[CH2:15][C:16]([C:18]1[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]2[CH2:27][CH2:28][N:29](C(=O)C(F)(F)F)[CH2:30][CH2:31][C:19]=12)=[O:17].[OH-].[Na+]>CN(C=O)C>[O:13]([CH2:15][C:16]([C:18]1[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]2[CH2:27][CH2:28][NH:29][CH2:30][CH2:31][C:19]=12)=[O:17])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 10272492HCID 10272492, compound2×

Product 1

HCID 9923094HCID 9923094, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(Chart E, Step 2): To a dry round bottom charged with a heterogeneous mixture of K2CO3 (40.77 mg, 0.30 mmol) and phenol (27.8 mg, 0.30 mmol) in DMF (1.5 mL) is added a solution of 1-[11-(2-bromoacetyl)-1,2,4,5-tetrahydro-3H-[1,4]diazepino[1,7-a]indol-3-yl]-2,2,2-trifluoro-1-ethanone in DMF (1.5 mL). After stirring at ambient temperature for 18 hours, aq. 1N NaOH (1 mL) is added at once to deprotect the indole in situ. The mixture is stirred for an hour then partitioned between water and ethyl acetate, the aqueous layer is extracted two more times with ethyl acetate. The organics are combined, dried with MgSO4, filtered and concentrated to 95 mg of a crude oil. The crude is purified by LC (230-400 silica gel) eluting with 0.5% NH4OH and 3.5% methanol in dichloromethane to afford 69 mg of 2-phenoxy-1-(2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-1-ethanone as a white solid. IR (drift) 1662, 1598, 1516, 1495, 1458, 1443, 1420, 1345, 1244, 1198, 1191, 1052, 975, 746, 688 cm−1.

Workup

  1. stirringThe mixture is stirred for an hour
  2. customthen partitioned between water and ethyl acetate
  3. extractionthe aqueous layer is extracted two more times with ethyl acetate
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to 95 mg of a crude oil
  7. customThe crude is purified by LC (230-400 silica gel)
  8. washeluting with 0.5% NH4OH and 3.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-c6f23da962d648eb8b3b480d70cfb226
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

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