Sodium hydride → HCID 59369799, compound

HRID 1662096Notes

Reaction equation

HRID 1662096 reaction equation
[CH3:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@@H:13]3[C@@H:11]([CH2:12]3)[C@H:10]2[CH2:15][OH:16])=[O:8])[N:6]=1.[H-].[Na+].[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1>C1COCC1>[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][O:16][CH2:15][C@H:10]2[N:9]([C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][C:4]=3[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:8])[CH2:14][C@@H:13]3[C@H:11]2[CH2:12]3)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 59369818HCID 59369818, compound

Product 1

HCID 59369799HCID 59369799, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of {(1R,2S,5S)-3-[(2-methyl-5-phenyl-1,3-thiazol-4-yl)carbonyl]-3-azabicyclo[3.1.0]hex-2-yl}methanol (0.025 g, 0.080 mmol) in THF (0.50 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 0.008 g, 0.206 mmol) followed by 4-fluorobenzylbromide (0.039 g, 0.206 mmol) and the system was stirred at 0° C. for 3 h. The mixture was then quenched with ice, extracted with EtOAc, purified using reverse phase conditions (5%→85% 0.1% TFA in water: 0.1% TFA in acetonitrile) followed by free basing with saturated sodium carbonate to afford the title compound as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.43-7.42 (m, 2H), 7.36-7.33 (m, 4H), 7.08-7.02 (m, 3H), 4.64 (m, 1H), 4.52 (m, 1H), 4.43 (m, 2H), 3.42 (m, 1H), 3.29 (m, 1H), 3.14 (m, 1H), 2.71 (s, 3H), 1.84 (m, 1H), 1.60 (m, 1H), 1.43 (m, 1H), 0.560 (m, 1H). HRMS [M+H] C24H23F1N2O2S1 calc'd 423.1537, found 423.1542.

Workup

  1. customThe mixture was then quenched with ice
  2. extractionextracted with EtOAc
  3. custompurified

Sources & evidence

ORD record
ord-aa62cbe384384feaa5c47b8a1577075c
Source dataset
uspto-grants-2011_10
Patent number
US08030495B2

Reaction notes

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