Lithiumtriethylborohydride → HCID 90089467, compound

HRID 1775733Notes

Reaction equation

HRID 1775733 reaction equation
Cl[CH2:2][C@@H:3]1[O:21][CH2:20][C@:6]2([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])[N:7]=[C:8]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[S:9][CH2:10][C@@H:5]2[CH2:4]1.C([BH-](CC)CC)C.[Li+]>O1CCCC1>[F:29][C:23]1[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:22]=1[C@:6]12[CH2:20][O:21][C@@H:3]([CH3:2])[CH2:4][C@H:5]1[CH2:10][S:9][C:8]([NH:11][C:12](=[O:19])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[N:7]2

Participants

4

Reactant 2

HCID 23664628LithiumtriethylborohydrideHCID 90089466HCID 90089466, compound

Product 1

HCID 90089467HCID 90089467, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-[(4aR,6R,8aS)-6-(Chloromethyl)-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C21) (1.88 g, 4.30 mmol) was dissolved in tetrahydrofuran and cooled to 0° C. Lithium triethylborohydride (1 M in tetrahydrofuran, 34.4 mL, 34.4 mmol) was added drop-wise, and the reaction mixture was allowed to warm to room temperature. After 18 hours, the reaction mixture was partitioned between aqueous sodium bicarbonate solution and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification using silica gel chromatography (Eluent: dichloromethane, followed by a gradient of 0% to 10% methanol in dichloromethane) provided the product as a white solid. Yield: 1.40 g, 3.48 mmol, 81%. LCMS m/z 403.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 12.29 (br s, 1H), 8.19-8.30 (br m, 2H), 7.48-7.54 (m, 1H), 7.37-7.48 (m, 3H), 6.84-6.96 (m, 2H), 4.15 (dd, J=12.2, 2.0 Hz, 1H), 3.77-3.84 (m, 1H), 3.77 (d, J=12.3 Hz, 1H), 3.09-3.19 (br m, 1H), 3.01 (dd, J=12.9, 4.1 Hz, 1H), 2.63 (dd, J=12.8, 2.8 Hz, 1H), 1.88-2.00 (m, 1H), 1.62-1.69 (m, 1H), 1.30 (d, J=6.2 Hz, 3H).

Workup

  1. temperatureto warm to room temperature
  2. customthe reaction mixture was partitioned between aqueous sodium bicarbonate solution and ethyl acetate
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification

Sources & evidence

ORD record
ord-78191b18bcbf4dbdb49f31c82a33620f
Source dataset
uspto-grants-2016_02
Patent number
US09260455B2

Reaction notes

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