Water → (S)-tert-Butyl 2-(4-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)phenyl)morpholine-4-carboxylate

HRID 710245Notes

Reaction equation

HRID 710245 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH:32]=[C:31](B(O)O)[CH:30]=[N:29]2)=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CC(N(C)C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH:32]=[C:31]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]4[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]4)=[CH:4][CH:3]=3)[CH:30]=[N:29]2)=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 467386841-(4-Fluorophenyl)pyrazole-4-boronic acidHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylate

Product 1

HCID 118412997(S)-tert-Butyl 2-(4-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)phenyl)morpholine-4-carboxylateYield 36.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (S)-tert-butyl 2-(4-bromophenyl)morpholine-4-carboxylate (100 mg, 0.29 mmol), 1-(4-fluorophenyl)-1H-pyrazole-4-ylboronic acid (60 mg, 0.29 mmol), tribasic potassium phosphate (124 mg, 0.585 mmol) and tetrakis(triphenylphosphine)palladium(0) (13.5 mg, 0.0117 mmol) in dimethylacetamide (2 ml) was placed in a microwave tube, closed and heated at 150° C. for 10 min using a microwave synthesizer (Personal Chemistry Emrys Optimizer). After cooling water (10 ml) was added, and the reaction mixture was extracted with ethyl acetate. The aqueous phase was re-extracted with ethyl acetate twice. The combined organic layers were dried (MgSO4) and evaporated. The residue was purified by flash chromatography (12 g silica gel, 10 to 50% ethyl acetate in heptane) to yield a light brown solid (45 mg, 36%). MS (ISP): 424.1 ([M+H]+).

Workup

  1. customwas placed in a microwave tube
  2. customclosed
  3. additionwas added
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. extractionThe aqueous phase was re-extracted with ethyl acetate twice
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by flash chromatography (12 g silica gel, 10 to 50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-952374cf15e04c39b34ce2b2d8e26f8b
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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