Tetrahydrofuran → (RS,SR)-2-benzenesulfonyl-2-(-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)-2-fluoro-N-methyl-N-(3-methyl-but-2-enyl)-acetamide

HRID 602809Notes

Reaction equation

HRID 602809 reaction equation
C(OC([N:8]1[C:20]2[CH2:19][CH:18]([C:21]([S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:29])=[O:28])([F:26])[C:22](=[O:25])[NH:23][CH3:24])[CH2:17][CH2:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[C:12]([Cl:36])[CH:13]=2)=O)(C)(C)C.[H-].[Na+].BrC[CH:41]=[C:42]([CH3:44])[CH3:43].[CH2:45]1COCC1>>[C:30]1([S:27]([C:21]([CH:18]2[CH2:17][CH2:16][C:15]3[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([Cl:36])[CH:13]=4)[NH:8][C:20]=3[CH2:19]2)([F:26])[C:22]([N:23]([CH3:45])[CH2:24][CH:41]=[C:42]([CH3:44])[CH3:43])=[O:25])(=[O:29])=[O:28])[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 700922-Butene, 1-bromo-3-methyl-HCID 67267476(RS,SR)-2-(benzenesulfonyl-fluoro-methylcarbamoyl-methyl)-6-chloro-1,2,3,4-tetrahydro-carbazole-9-carboxylic acid tert-butyl ester

Product 1

HCID 46898301(RS,SR)-2-benzenesulfonyl-2-(-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)-2-fluoro-N-methyl-N-(3-methyl-but-2-enyl)-acetamideYield 19%

Procedure

To a stirred solution of 60 mg (0.11 mmol) of (RS,SR)-2-(benzenesulfonyl-fluoro-methylcarbamoyl-methyl)-6-chloro-1,2,3,4-tetrahydro-carbazole-9-carboxylic acid tert-butyl ester in 3 mL THF was added on 7 mg NaH (60% in oil, 0.165 mmol, 1.5 eq) at 0° C. The reaction mixture was stirred for 40 minutes and then, 52 μL (0.22 mmol, 2 eq) 1-bromo-3-methyl-but-2-ene (1 mL in THF) was added and the reaction mixture was stirred for 2 hours at 0° C. and then overnight at RT. The solvent was evaporated. Then, 1 mL CH2Cl2 was added and after dissolution, 1 mL TFA and 1 mL CH2Cl2 were added at RT. The reaction mixture was stirred overnight. The solvent was then evaporated and purification by prep. HPLC gave 9 mg (19%) of (RS,SR)-2-benzenesulfonyl-2-(-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)-2-fluoro-N-methyl-N-(3-methyl-but-2-enyl)-acetamide as a white solid, MS: 503 (MH+).

Workup

  1. stirringthe reaction mixture was stirred for 2 hours at 0° C.
  2. customovernight
  3. customat RT
  4. customThe solvent was evaporated
  5. additionThen, 1 mL CH2Cl2 was added
  6. dissolutionafter dissolution, 1 mL TFA and 1 mL CH2Cl2
  7. additionwere added at RT
  8. stirringThe reaction mixture was stirred overnight
  9. customThe solvent was then evaporated
  10. custompurification by prep

Sources & evidence

ORD record
ord-9e13a9190ded4781b4456f7d0cb1071c
Source dataset
uspto-grants-2011_03
Patent number
US07906546B2

Reaction notes

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