Hydrochloric Acid → HCID 59753010, compound

HRID 1909764Notes

Reaction equation

HRID 1909764 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3([C:31]#N)[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.CC(C[AlH]CC(C)C)C.Cl.C([O-])(O)=[O:44].[Na+]>C1(C)C=CC=CC=1>[CH3:6][N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([O:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3([CH:31]=[O:44])[CH2:29][CH2:30]3)=[CH:26][CH:27]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14487Diisobutylaluminum hydrideHCID 516892Sodium BicarbonateHCID 69002504HCID 69002504, compound

Product 1

HCID 59753010HCID 59753010, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 25 mL vial which contained a solution of (R)-2-{4-[4-(1-Cyano-cyclopropyl)-phenoxy]-phenoxymethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester 3 (110 mg, 0.25 mmol) in anhydrous toluene (2 mL) were added DIBAL (0.5 mL 1M in hexane)) at −78° C. under the atmosphere of argon. The reaction mixture was allowed to warm to rt and stir at rt for 0.5 h. After cooled to ° C., 0.5 mL HCl was added to the mixture, the mixture was stirred for 10 min and then was neutralized with the addition of sat. NaHCO3 solution. This mixture was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL), brine (30 mL) and dried over anhydrous Na2SO4. The solvent was removed under vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford the title product, (50 mg, 65%); LCMS; 95%, APCI+ Calcd: 351.5, found m/z: 353.1 (M+1); 1HNMR (400 MHz, CDCl3); δ 1.36-1.39 (m, 2H), 1.54-1.56 (m, 2H), 1.70-2.10 (m, 4H), 2.26-2.33 (m, 1H), 2.48 (s, 3H), 2.60-2.70 (m, 1H), 3.09-3.13 (m, 1H), 3.85-3.99 (m, 2H), 6.88-6.93 (m, 4H), 6.95-6.99 (m, 2H), 7.20-7.30 (m, 2H) 9.22 (s, 1H),

Workup

  1. temperatureAfter cooled
  2. stirringthe mixture was stirred for 10 min
  3. extractionThis mixture was extracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with water (2×30 mL), brine (30 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe solvent was removed under vacuo
  7. customto obtain the crude product which
  8. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-3d81af5d5c7246bdb8cda60d64cc494e
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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