Water → (4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol

HRID 1912551Notes

Reaction equation

HRID 1912551 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[C:16]([C:17](OC)=[O:18])=[C:15]([CH3:21])[N:14]=[C:13]4[N:22]([CH2:25][C:26]5[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=5)[CH:23]=[CH:24][C:12]=34)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[O:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[C:16]([CH2:17][OH:18])=[C:15]([CH3:21])[N:14]=[C:13]4[N:22]([CH2:25][C:26]5[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=5)[CH:23]=[CH:24][C:12]=34)=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 71209465methyl 4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Product 1

HCID 71209165(4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

An ice cold solution of methyl 4-(chroman-6-yl)-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (1.019 g, 2.272 mmol) in tetrahydrofuran (THF) (10 mL) was treated with lithium aluminum hydride (1.0 M solution in tetrahydrofuran) (6.82 mL, 6.82 mmol) and the mixture was stirred at ambient temperature for 3 hours. The mixture was cooled to 0° C., water (259 uL) was added and the mixture was stirred 5 minutes. Then 15% NaOH (259 uL) was added and the mixture was stirred for 5 minutes. Finally, water (777 uL) was added, the mixture was diluted with ethyl acetate and then stirred 10 minutes. The mixture was filtered over Celite™ and the filtrate was concentrated to afford an off-white residue: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.24-7.15 (m, 2 H), 7.14-7.01 (m, 3 H), 6.98 (dt, J=2.0, 4.0 Hz, 1 H), 6.91 (d, J=8.2 Hz, 1 H), 6.26 (d, J=3.5 Hz, 1 H), 5.45 (s, 2 H), 4.74 (d, J=3.9 Hz, 2 H), 4.35-4.21 (m, 2 H), 2.93-2.74 (m, 5 H), 2.18-1.96 (m, 2 H); LC/MS (m/z) ES+=421 (M+1).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringthe mixture was stirred 5 minutes
  3. stirringthe mixture was stirred for 5 minutes
  4. stirringstirred 10 minutes
  5. filtrationThe mixture was filtered over Celite™
  6. concentrationthe filtrate was concentrated
  7. customto afford an off-white residue

Sources & evidence

ORD record
ord-c4a09dfe23eb4cd7be2458764e53287a
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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