Water → HCID 71209178, compound

HRID 1912599Notes

Reaction equation

HRID 1912599 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:21])=[C:13]([C:16](OCC)=[O:17])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1.CC(C[AlH]CC(C)C)C.O.[OH-].[Na+].O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][N:6]1[C:10]2=[N:11][C:12]([CH3:21])=[C:13]([CH2:16][OH:17])[C:14]([I:15])=[C:9]2[CH:8]=[CH:7]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14487Diisobutylaluminum hydride2×HCID 23719242Sodium hydroxide--water (1/1/1)HCID 71209351HCID 71209351, compound

Product 1

HCID 71209178HCID 71209178, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (6.5 g, 11.40 mmol) in anhydrous DCM (110 mL) was cooled to −55° C. and then DIBAL-H (22.80 mL, 22.80 mmol) (1M/toluene) was added dropwise in ˜20 min and the mixture was allowed to warm to 0° C. in 1 h and kept at 0° C. for 1 h. More DIBAL-H (12 mL, 12 mmol) was added and stirring at 0° C. continued for 1 h. The mixture was cooled to 0° C. and water (1.4 mL) was added slowly followed by 15% NaOH/water (1.4 mL) and water (3.5 mL). The mixture was stirred at RT for 15 min then filtered through a path of celite washing with dichloromethane. The filtrate was concentrated and co-evaporated with MeCN, dried in vacuo to provide (1-(3,4-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol (5.0 g, 9.66 mmol, 85% yield) as an orange solid. 1H NMR and LCMS are consistent with proposed structure. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.80 (br s, 1 H), 2.83 (s, 3 H), 5.02 (d, J=2.15 Hz, 2 H), 5.40 (s, 2 H), 6.35 (d, J=3.51 Hz, 1 H), 6.92-7.12 (m, 3 H), 7.13 (d, J=3.51 Hz, 1 H); LCMS (m/z) ES+=415 (M+1).

Workup

  1. waitcontinued for 1 h
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringThe mixture was stirred at RT for 15 min
  4. filtrationthen filtered through a path
  5. washof celite washing with dichloromethane
  6. concentrationThe filtrate was concentrated
  7. customdried in vacuo

Sources & evidence

ORD record
ord-3f9c3608b7e14fd4a7bd71a70b8a9539
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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