Imidazole → HCID 123410153, compound

HRID 596027Notes

Reaction equation

HRID 596027 reaction equation
[F:1][C@@H:2]1[C@@H:7]([OH:8])[CH2:6][CH2:5][C@@H:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3]1.[CH3:14][C:15]([Si:18](Cl)([CH3:20])[CH3:19])([CH3:17])[CH3:16].C(Cl)Cl.N1C=CN=C1>O>[Si:18]([O:8][C@H:7]1[CH2:6][CH2:5][C@@H:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3][C@@H:2]1[F:1])([C:15]([CH3:17])([CH3:16])[CH3:14])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6344DichloromethaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 118054566HCID 118054566, compound

Product 1

HCID 123410153HCID 123410153, compoundYield 75.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 500 mL flask was added (1R,3S,4S)-ethyl 3-fluoro-4-hydroxycyclohexane-carboxylate (17 g, 89.3 mmol, 97.9% ee), TBSCl (17.5 g, 116.1 mmol) and DCM (200 mL). Imidazole (12.1 g, 178 mmol) was added to the resultant clear solution and the reaction mixture was stirred for 16 hours. Water (100 mL) was added and the mixture was stirred for a further 10 minutes. The phases were separated and the organic layer was washed with water (100 mL) and concentrated under reduced pressure (40±5° C., 50˜250 mbar). Purification by flash chromatography on silica eluting with a mixture of heptane and ethyl acetate (100:1) gave (1R,3S,4S)-ethyl 4-((tert-butyldimethylsilyl)oxy)-3-fluorocyclohexanecarboxylate as a colorless oil (20.6 g, yield 75.7%). 1H NMR (400 MHz, DMSO-d6): 4.38˜4.52 (m, 1H), 4.03˜4.08 (dd, J=12 Hz, J=8 Hz, 2H), 3.77˜3.81 (m, 1H), 2.54˜2.60 (m, 1H), 1.93˜2.06 (m, 1H), 1.58˜1.86 (m, 4H), 1.46˜1.50 (m, 1H), 1.17˜1.20 (t, J=12 Hz, J=6 Hz, 3H), 0.85 (s, 9H), 0.03˜0.04 (d, J=4 Hz, 8H), [M+H]+=305.1 via GC-MS (Instrument: Agilent Technologies, GC 6890N, MS 5975C. GC conditions: Column: HP—5 MS, Capillary: 30.0 m×250 μm×0.25 μm, Detecor parameters: Temperature: 350° C., Flow H2: 40 mL/min, Air flow: 400 mL/min, Makeup (He): 40 mL/min. Injector parameters: temperature: 200° C. Split ratio: 100:1. Carrier gas: He, Flow: 2.0 mL/min, Mode: Constant flow. Oven parameters: 0 min, 50° C.; 2.0 min, 50° C.; 5.33 min, 100° C.; 15.83 min, 270° C. Injection volume: 1 μL, Syringe wash solvent: acetonitrile. MS conditions: Volt: 70 EV, Scan range: m/z=50˜550)

Workup

  1. stirringthe mixture was stirred for a further 10 minutes
  2. customThe phases were separated
  3. washthe organic layer was washed with water (100 mL)
  4. concentrationconcentrated under reduced pressure (40±5° C., 50˜250 mbar)
  5. customPurification by flash chromatography on silica eluting
  6. additionwith a mixture of heptane and ethyl acetate (100:1)

Sources & evidence

ORD record
ord-a1fec0a3479d4021a0d26479cfce4baa
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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