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Water → 3-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-indole-1-carboxylic acid tert-butyl ester

HRID 1667624
Notes
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Reaction equation

HRID 1667624 reaction equation
Br[C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[CH:5]=[CH:4][N:3]=1.[C:23]([O:27][C:28]([N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C=CC=CC=1.C(O)C.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.CCOC(C)=O>[C:23]([O:27][C:28]([N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([C:2]2[CH:7]=[C:6]([C@@H:8]3[CH2:12][CH2:11][CH2:10][N:9]3[C@@H:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH3:14])[CH:5]=[CH:4][N:3]=2)=[CH:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 49758860tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylateHCID 581118522-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

Product 1

HCID 668898973-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-indole-1-carboxylic acid tert-butyl ester
Yield 79.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 2-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (160 mg, 0.44 mmol) in a mixture of toluene (9 mL) and ethanol (3 mL) are added 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indole-1-carboxylic acid tert-butyl ester (228 mg, 0.66 mmol), Pd(PPh3)4 (51 mg, 0.04 mmol) and sodium carbonate (2N) (0.7 mL, 1.40 mmol). The reaction mixture is stirred at 85° C. overnight, cooled to room temperature. Water and EtOAc are added to the mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 10%˜90%) to give 3-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-indole-1-carboxylic acid tert-butyl ester as a yellow solid (175 mg, 79%). M/Z=498.32 [M+1]

Workup

  1. temperaturecooled to room temperature
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 10%˜90%)

Sources & evidence

ORD record
ord-6b0c08047353450a9a3fa93064579068
Source dataset
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08044209B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes