Tetrabutylammonium Fluoride → HCID 71727133, compound

HRID 2365817Notes

Reaction equation

HRID 2365817 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[N:26]=2)=[CH:21][C:20]1=[O:38])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:10]([N:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][CH:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[N:26]=3)=[CH:21][C:20]2=[O:38])[CH2:9][OH:8])=[CH:12][C:13]=1[F:18]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86696668HCID 86696668, compound

Product 1

HCID 71727133HCID 71727133, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (6.00 g, 10.7 mmol) in THF (20 mL) was treated with tetrabutyl ammonium fluoride (12.9 mL, 12.9 mmol) at room temperature for 30 minutes. The reaction mixture was concentrated, and the residue was taken up with ethyl acetate and water. The organic layer was washed with water (1×). The combined organics were dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with ethyl acetate to give (S)-1-(1-(4-chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((tetrahydro-2H-pyran-4-ylamino))pyrimidin-4-yl)pyridin-2(1H)-one as a solid (4.14 g, 87%; 96% enantiomeric excess (“e.e.”) by chiral HPLC (Chiral Tech, column OJ-H, 4.6 mm×250 mm, 5 u, 30% ethanol/70% hexanes, 1 mL/minute)). 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J=5.0 Hz, 1H), 7.40 (m, 2H), 7.20 (m, 2H), 7.10 (d, J=8.2 Hz, 1H), 6.88 (d, J=5.0 Hz, 1H), 6.78 (m, 1H), 6.20 (m, 1H), 5.16 (d, J=8.0 Hz, 1H), 4.31 (m, 2H), 4.10 (m, 1H), 4.00 (m, 2H), 3.55 (m, 2H), 2.74 (br, s, 1H), 2.06 (m, 2H), 1.58 (m, 2H); m/z (APCI-pos) M+1=445.1, 447.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washThe organic layer was washed with water (1×)
  3. customThe combined organics were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified via column chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-294c66f322304b68a7c576ba83e6d2d4
Source dataset
uspto-grants-2014_04
Patent number
US08697715B2

Reaction notes

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