Methanol → 2-[2-Fluoro-4-(4-hydroxy-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

HRID 1027415Notes

Reaction equation

HRID 1027415 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:39][CH2:38][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]4[CH2:28][CH2:27][CH:26]([O:29][Si](C(C)(C)C)(C)C)[CH2:25][CH2:24]4)=[CH:19][C:18]=3[F:37])[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].CO>C1COCC1.C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]4[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25][CH2:24]4)=[CH:19][C:18]=3[F:37])[CH2:13][CH2:12]2)[CH2:38][CH2:39]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 887MethanolHCID 2724141Tetrabutylammonium FluorideHCID 674789912-{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenyl}-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

Product 1

HCID 674790852-[2-Fluoro-4-(4-hydroxy-cyclohexyl)-phenyl]-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

2-{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohexyl]-2-fluoro-phenyl}-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (720 mg, 1.29 mmol) was dissolved in THF (10 mL). To this solution at rt was added TBAF (1M in THF) (2 mL, 2 mmol, 1.5 equiv.). The reaction mixture was then heated to 60° C. (bath set) for 5 h. The reaction was complete (TLC, 5% MeOH in DCM). The reaction was diluted with EtOAc (5 mL), quenched with NaHCO3 (saturated aqueous solution, 5 mL). The two layers were separated and the aq. layer was extracted with EtOAc (15 mL×2). The EtOAc solution was combined, washed with brine (10 mL), and dried over K2CO3, filtered, and concentrated. The crude product was purified on a silica gel column eluted with 5% MeOH in DCM to afford 0.53 g (93% yield) of the title compound as a white solid.

Workup

  1. customquenched with NaHCO3 (saturated aqueous solution, 5 mL)
  2. customThe two layers were separated
  3. extractionthe aq. layer was extracted with EtOAc (15 mL×2)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over K2CO3
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified on a silica gel column
  9. washeluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-0591f8e7151348dabab0c65dac4170c8
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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