Water → (R)-tert-butyl 1-(4-fluorophenyl)-4a-(R/S)-(hydroxy(l-methyl-1H-pyrazol-4-yl)methyl)-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-6(4H)-carboxylate

HRID 920637Notes

Reaction equation

HRID 920637 reaction equation
C([Li])CCC.I[C:7]1[CH:8]=[N:9][N:10]([CH3:12])[CH:11]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:24]3[CH:25]=[C:26]4[C@:31]([CH:33]=[O:34])([CH2:32][C:23]=3[CH:22]=[N:21]2)[CH2:30][N:29]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:28][CH2:27]4)=[CH:16][CH:15]=1.O>O1CCCC1.ClCCl>[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:24]3[CH:25]=[C:26]4[C:31]([C@@H:33]([OH:34])[C:7]5[CH:8]=[N:9][N:10]([CH3:12])[CH:11]=5)([CH2:32][C:23]=3[CH:22]=[N:21]2)[CH2:30][N:29]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:28][CH2:27]4)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27347731-Methyl-4-iodo-1H-pyrazoleHCID 89954836(R)-tert-butyl 1-(4-fluorophenyl)-4a-formyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-6(4H)-carboxylateHCID 178418339Butyllithium2×

Product 1

HCID 89954439(R)-tert-butyl 1-(4-fluorophenyl)-4a-(R/S)-(hydroxy(l-methyl-1H-pyrazol-4-yl)methyl)-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-6(4H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A second reaction was performed with inverse addition of n-butyl lithium. To a solution of 4-iodo-1-methyl-1H-pyrazole (157 mg, 0.755 mmol) in tetrahydrofuran (2 mL) was added n-butyl lithium (2.5 M in Hexanes) (312 μl, 0.780 mmol) at −78° C. The mixture was stirred at this temperature for 1 hour, then a solution of (R)-tert-butyl 1-(4-fluorophenyl)-4a-formyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-6(4H)-carboxylate (100 mg, 0.252 mmol) in tetrahydrofuran (1 mL) was added dropwise to the reaction mixture. The mixture was stirred at this temperature for 30 minutes. Water (6 mL) and dichloromethane (8 mL) were added and the phases were separated using a phase separator cartridge. The solvent was removed in vacuo to give an orange oil, with a similar composition to the previous reaction product according to LC/MS analysis.

Workup

  1. customA second reaction
  2. stirringThe mixture was stirred at this temperature for 30 minutes
  3. customthe phases were separated
  4. customThe solvent was removed in vacuo
  5. customto give an orange oil

Sources & evidence

ORD record
ord-418a6359eb2846dba581b6567f0e5f89
Source dataset
uspto-grants-2016_03
Patent number
US09273047B2

Reaction notes

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