Potassium Carbonate → (R)-tert-Butyl 4-(2-(1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)carbamate

HRID 1689504Notes

Reaction equation

HRID 1689504 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C@H:8]([C:45]1[C:53]2[S:52][C:51](=[O:54])[NH:50][C:49]=2[C:48]([OH:55])=[CH:47][CH:46]=1)[CH2:9][N:10]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]2[CH2:44][CH2:43][C:31]3([O:36][CH2:35][CH2:34][N:33](C(=O)C(F)(F)F)[CH2:32]3)[CH2:30][CH2:29]2)=[CH:21][CH:20]=1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14]>O.CO>[O:36]1[C:31]2([CH2:43][CH2:44][N:28]([CH2:27][CH2:26][O:25][C:22]3[CH:21]=[CH:20][C:19]([CH2:18][N:10]([CH2:9][C@H:8]([OH:7])[C:45]4[C:53]5[S:52][C:51](=[O:54])[NH:50][C:49]=5[C:48]([OH:55])=[CH:47][CH:46]=4)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:24][CH:23]=3)[CH2:29][CH2:30]2)[CH2:32][NH:33][CH2:34][CH2:35]1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 57989007(R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(2,2,2-trifluoroacetyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

Product 1

HCID 57989223(R)-tert-Butyl 4-(2-(1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)carbamate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of potassium carbonate (240 mg) in water (35 mL) was added to a solution of (R)-tert-butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(2,2,2-trifluoroacetyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate (examples 223-263, step a) (725 mg) in MeOH (35 mL). The resulting mixture was stirred at RT for 5 h. Methanol was removed by evaporation under a stream of nitrogen keeping the reaction mixture at 25° C. Water (20 mL) and brine (30 mL) were added and the mixture was extracted with ethyl acetate (7×30 mL). The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-20% (2M NH3 in MeOH)/DCM to give the subtitled compound as a white solid. Yield 385 mg.

Workup

  1. customMethanol was removed by evaporation under a stream of nitrogen keeping the reaction mixture at 25° C
  2. additionWater (20 mL) and brine (30 mL) were added
  3. extractionthe mixture was extracted with ethyl acetate (7×30 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-20% (2M NH3 in MeOH)/DCM

Sources & evidence

ORD record
ord-3109d699472b4e5a8bc16448dd4757b4
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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