Sodium Carbonate Monohydrate → HCID 71209350, compound

HRID 1912603Notes

Reaction equation

HRID 1912603 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:22])=[C:13]([C:16](=[O:21])[C:17]([O:19][CH3:20])=[O:18])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1.CCO.C(=O)=O.[B]1OC2C(=CC=CC=2)O1.C([O-])([O-])=O.[Na+].[Na+].O>C1(C)C=CC=CC=1.CCOC(C)=O.O>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:22])=[C:13]([C@H:16]([OH:21])[C:17]([O:19][CH3:20])=[O:18])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1

Participants

8

Reactant 4

HCID 2735133Sodium Carbonate MonohydrateHCID 6327445BenzcatechinboraneHCID 19604758Methanedione--ethanol (1/1)HCID 71209353HCID 71209353, compound

Product 1

HCID 71209350HCID 71209350, compoundYield 87.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of methyl 2-(1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-oxoacetate (845 mg, 1.528 mmol) in anhydrous toluene (13 mL) under nitrogen atmosphere was added (R)-CBS (0.382 mL, 0.382 mmol) (1M/toluene) and the mixture was cooled to −35° C. (EtOH/dry ice); catecholborane (4.74 mL, 4.74 mmol) (1M/THF) was slowly added dropwise over 1 h 15 min and then allowed to warm to −10° C. in ˜30 min and stirred at this temperature for 1 h. 2M Na2CO3/water and EtOAc was added and the mixture was stirred at RT for 5 min., diluted with EtOAc and water. The organic phase was washed with 2M Na2CO3, 1M NaOH/water, saturated NH4Cl, brine, dried (Na2SO4), concentrated, and purified by column chromatography to provide (S)-methyl 2-(1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate (663 mg, 1.334 mmol, 87% yield) as a yellowish foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.69 (s, 3 H), 3.46 (d, J=2.35 Hz, 1 H), 3.81 (s, 3 H), 5.40-5.62 (m, 2 H), 5.91 (d, J=2.15 Hz, 1 H), 6.41 (d, J=3.52 Hz, 1 H), 6.93-7.20 (m, 4 H); LCMS (m/z) ES+=473 (M+1). Chiral HPLC (Whelk 0 SS 4.6×250 mm column with 25% IPA in hexane. UV was monitored at 215, 254, and 280 nm.): 94% ee.

Workup

  1. stirringthe mixture was stirred at RT for 5 min.
  2. washThe organic phase was washed with 2M Na2CO3, 1M NaOH/water, saturated NH4Cl, brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-ddffcd2f2ecf49118e24559e4edd565c
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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