Ethyl Acetate → HCID 86714784, compound

HRID 1055137Notes

Reaction equation

HRID 1055137 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:11][C:12]1[N:17]=[C:16]([NH:18][C@@H:19]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:20][CH:21]=O)[C:15]([F:27])=[CH:14][N:13]=1.[CH3:28]COC(C)=O.[NH4+].[Cl-]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[Cl:11][C:12]1[N:17]=[C:16]([NH:18][C@H:19]([CH2:20][CH:21]=[CH2:28])[C:23]([CH3:26])([CH3:25])[CH3:24])[C:15]([F:27])=[CH:14][N:13]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 86714785HCID 86714785, compound

Product 1

HCID 86714784HCID 86714784, compound

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl(triphenyl)phosphonium bromide (0.983 g, 2.753 mmol) in THF (40 mL) was added LiHMDS (2.753 mL of 1 M solution, 2.753 mmol). The reaction mixture was stirred at room temperature for 1 hour. A solution of (3R)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-4,4-dimethyl-pentanal (0.550 g, 2.118 mmol) in THF (20 mL) was added to the reaction mixture resulting in significant precipitate formation. The reaction mixture was stirred at room temperature for 45 minutes. The reaction mixture was diluted into EtOAc and aqueous saturated NH4Cl solution. The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (EtOAc/Hexanes) to afford 180 mg of desired product: 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J =2.8 Hz, 1H), 5.76-5.60 (m, 1H), 5.05-4.91 (m, 2H), 4.82 (t, J=22.1 Hz, 1H), 4.26-4.11 (m, 1H), 2.58-2.48 (m, 1H), 2.07-1.92 (m, 1H), 0.94 (s, 9H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.60 minutes (M+H) 258.38.

Workup

  1. customresulting in significant precipitate formation
  2. stirringThe reaction mixture was stirred at room temperature for 45 minutes
  3. customThe organic phase was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by silica gel chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-e9a766b63acf45d8b36b9faa775c75cd
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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