Potassium Carbonate → tert-Butyl (2S,4S)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate

HRID 906469Notes

Reaction equation

HRID 906469 reaction equation
[BH4-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH:8]=[C:7]2[SH:15].[Si:16]([O:33][CH2:34][C@@H:35]1[CH2:40][C@H:39](OS(C)(=O)=O)[CH2:38][CH2:37][N:36]1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH:8]=[C:7]2[S:15][C@H:39]1[CH2:38][CH2:37][N:36]([C:46]([O:48][C:49]([CH3:51])([CH3:50])[CH3:52])=[O:47])[C@H:35]([CH2:34][O:33][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:40]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 4311764Sodium borohydrideHCID 57439914HCID 57439914, compoundHCID 86640979tert-Butyl (2S,4R)-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(methylsulfonyl)-oxy]piperidine-1-carboxylate

Product 1

HCID 86640978tert-Butyl (2S,4S)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylateYield 45.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium borohydride (97 mg) was added to a degassed solution of 6-bromo-4-sulfanylisoquinolin-1(2H)-one (Example 58a, 0.54 g) in ethanol (20 mL) at room temperature with effervescence. The resulting mixture was stirred at room temperature for 10 min before being heating to 85° C. A degassed solution of tert-Butyl (2S,4R)-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(methylsulfonyl)-oxy]piperidine-1-carboxylate (Example 67d, 1.17 g) in ethanol (3 mL) and potassium carbonate (0.353 g) were added to the orange solution and the reaction was heated for 1 h, cooled to room temperature and concentrated in vacuo. Purification (SiO2 chromatography, elution gradient 25% to 40% ethyl acetate in isohexane) afforded the subtitle product (0.68 g) as a white foam.

Workup

  1. temperaturebefore being heating to 85° C
  2. temperaturethe reaction was heated for 1 h
  3. temperaturecooled to room temperature
  4. concentrationconcentrated in vacuo
  5. customPurification (SiO2 chromatography, elution gradient 25% to 40% ethyl acetate in isohexane)

Sources & evidence

ORD record
ord-f58de0166f7e448b81bbc83c80061711
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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