HCID 22733850, compound → HCID 22733852, compound

HRID 2084599Notes

Reaction equation

HRID 2084599 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C:17](=[O:37])[C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])[C:19]=3[O:35][CH3:36])[CH2:13][CH2:12]2)=O)=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:11]2[CH2:12][CH2:13][CH:14]([CH:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([CH:26]([CH3:28])[CH3:27])([CH:32]([CH3:33])[CH3:34])[CH:29]([CH3:30])[CH3:31])[C:19]=3[O:35][CH3:36])[OH:37])[CH2:15][CH2:16]2)=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 22733850HCID 22733850, compound

Product 1

HCID 22733852HCID 22733852, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of 2-(4-Fluoro-phenyl)-1-[4-(2-methoxy-3-triisopropylsilanyloxy-benzoyl)-piperidin-1-yl]-ethanone, Example 1A (262 g, 0.496 mol) in toluene (3.8 L) at −38° C. add (R)-methyloxoazaborolidine (150 mL, 0.15 mol, of 1M solution in toluene), follow with the addition of borane dimethylsulfide complex (750 mL of a 2M solution in toluene, 1.5 mol), over a 2 h period at −30° C. Stir between −25° C. to −28° C. overnight and then allow the reaction to warm to ambient temperature over a 2 h period. Slowly add MeOH (500 mL) over al h period and then concentrate the solution to obtain 363 g of yellow oil. Add MeOH (1.8 L) to the oil and concentrate under reduced pressure at 80° C. to obtain 341 g of a yellow oil. Purify the oil by plug filtration through silica gel eluting with 1:1 MeOH/CHCl3. Combine and concentrate the desired fractions to obtain 250 g of product. Further purify the product by column chromatography over silica gel eluting with 1:3 EtOAc/hexane (20 L), 1:1 EtOAc/hexane (20 L) and 1:1 CHCl3/MeOH (40 L). Collect and concentrate like fractions to obtain 214 g of oil. Dissolve the oil in CHCl3 (500 mL)/toluene (600 mL), dry (MgSO4) and concentrate to obtain 207 g of the title compound as a foam.

Workup

  1. customat −38° C.
  2. customthe reaction
  3. concentrationSlowly add MeOH (500 mL) over al h period and then concentrate the solution

Sources & evidence

ORD record
ord-16db512bf5954e8bae4bcc06f9c33b96
Source dataset
uspto-grants-2004_04
Patent number
US06716986B2

Reaction notes

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