Diisobutylaluminum hydride → HCID 178521038, compound

HRID 1163186Notes

Reaction equation

HRID 1163186 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:8][C@H:7]([N:9]2[C:13]3[N:14]=[CH:15][N:16]=[C:17]([Cl:18])[C:12]=3[C:11]([I:19])=[CH:10]2)[CH2:6]1)=O.C(=O)=O.CC(C)=O.CC(C[AlH]CC(C)C)C>C(Cl)Cl>[Cl:18][C:17]1[C:12]2[C:11]([I:19])=[CH:10][N:9]([C@H:7]3[CH2:6][C@H:5]([CH2:3][OH:2])[CH2:8]3)[C:13]=2[N:14]=[CH:15][N:16]=1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 18522661Acetone cardice2×HCID 178501319HCID 178501319, compound

Product 1

HCID 178521038HCID 178521038, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-3-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutanecarboxylic acid methyl ester (trans/cis=5:1) (116.5 mg, 0.297 mmol) in CH2Cl2 (5 mL), cooled by dry ice/acetone, was added DIBAL (1M in toluene, 0.65 mL, 0.65 mmol). After 40 min, the dry ice/acetone bath was replaced with and ice/water bath. The reaction was quenched 2 h later by adding potassium sodium tartrate solution, the mixture was extracted with CH2Cl2 (3×20 mL), the combined extracts were washed with NaHCO3 solution and brine, dried over MgSO4, filtered, and concentrated to give the target compound as 5:1 trans/cis mixture. This material was chromatographed on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 (1-8)→CH2Cl2:EtOAc 9:1 (9-19)→CH2Cl2:EtOAc 5:1 (20-47)→CH2Cl2:EtOAc 3:1 (48-60)] to give the title compound with trans/cis=25:1. A forerunning fraction enriched with the cis isomer was also isolated. 1H NMR (CDCl3, 400 MHz) δ 2.42-2.57 (m, 2H), 2.58-2.72 (m, 3H), 3.85 (brs, 2H), 5.36-5.48 (mc, 1H), 7.61 (s, 1H), 8.60 (s, 1H). MS (ES+): m/z 363.9/365.9 (100/36) [MH+]. HPLC: tR=3.0 min (OpenLynx, polar—5 min).

Workup

  1. customThe reaction was quenched 2 h later
  2. additionby adding potassium sodium tartrate solution
  3. extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
  4. washthe combined extracts were washed with NaHCO3 solution and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the target compound as 5:1 trans/cis mixture
  9. customThis material was chromatographed on silica gel [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 (1-8)→CH2Cl2:EtOAc 9:1 (9-19)→CH2Cl2:EtOAc 5:1 (20-47)→CH2Cl2:EtOAc 3:1 (48-60)]

Sources & evidence

ORD record
ord-a35f6bfe69384d03ae943245cb5c2345
Source dataset
uspto-grants-2010_10
Patent number
US07820662B2

Reaction notes

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