Hydrochloric Acid → (3R)-4,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanal

HRID 1817667Notes

Reaction equation

HRID 1817667 reaction equation
[F:1][C:2]([F:30])([F:29])[C@H:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#N.[H-].C([Al+]CC(C)C)C(C)C.C[OH:42].Cl>C(Cl)Cl.O>[F:1][C:2]([F:29])([F:30])[C@H:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:27])[CH3:28])[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][CH:5]=[O:42]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 21225700DiisobutylaluminumhydrideHCID 57478054(3R)-4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

Product 1

HCID 59159509(3R)-4,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanalYield 84.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-47.5 °C

Procedure

To a −70° C. solution of (3R)-4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (1.06 g, 0.00243 mol) (see, Example 93, Step1) in DCM (10 mL, 0.2 mol) was added 1.0 M diisobutylaluminum hydride in DCM (4.8 mL). The resulting mixture was stirred for 3 h and allowed to warm during this time interval from −70 to −25° C., after which the reaction was cooled back at −70° C. Methanol (1.5 mL, 0.037 mol) was added, followed by 2.0 M HCl in water (15 mL). Insoluble material was then filtered from the reaction mixture. The organic filtrate was washed sequentially with: 2.0 M HCl in water, water and saturated aqueous NaCl. The washed organic phase was dried over sodium sulfate and was concentrated using a rotory evaporator to give 0.58 g of the crude product as a pale yellow foam/solid. The crude product was chromatographed with 0-80% ethyl acetate/hexanes to give the purified product (0.9 g) as a pale orange oil (47% yield).

Workup

  1. temperatureafter which the reaction was cooled back at −70° C
  2. filtrationInsoluble material was then filtered from the reaction mixture
  3. washThe organic filtrate was washed sequentially with: 2.0 M HCl in water, water and saturated aqueous NaCl
  4. dry with materialThe washed organic phase was dried over sodium sulfate
  5. concentrationwas concentrated
  6. customa rotory evaporator
  7. customto give 0.58 g of the crude product as a pale yellow foam/solid
  8. customThe crude product was chromatographed with 0-80% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1a39dcce62a64d0caf267e07081c2308
Source dataset
uspto-grants-2009_10
Patent number
US07598257B2

Reaction notes

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