Dimethyl Sulfoxide → HCID 118207506, compound

HRID 1507246Notes

Reaction equation

HRID 1507246 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C@@H:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C@H:26]2[OH:38])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[CH2:27][C:26]2=[O:38])=[CH:21][CH:20]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 97107398HCID 97107398, compound

Product 1

HCID 118207506HCID 118207506, compoundYield 72.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DMSO (3.7 mL, 52 mmol) in 50 mL of DCM under nitrogen at −78° C. was added oxalyl chloride (4.45 mL, 51 mmol). The mixture was stirred for 10 minutes after the completion of the addition. Then a solution of (±)-rel-(3S,4S)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-hydroxypiperidine-1-carboxylate (from Example 50, step D, 6.5 g, 17 mmol) in 50 mL of DCM was added and the mixture was stirred in the cold for a further 90 minutes. The reaction was then quenched by the addition of 11.8 mL of triethylamine (85 mmol) and allowed to warm up to rt. The mixture was then partitioned between 200 mL brine and 200 mL DCM. The layers were separated, and the organic layer was dried over Na2SO4, filtered, and concentrated. The residue was subjected to column chromatography on 48 g of basic alumina eluting with 8% ethyl acetate/hexanes to afford 4.7 g (67%) of racemic tert-butyl 4-(4-(benzyloxy)phenyl)-3-oxopiperidine-1-carboxylate. LCMS (method F) RT 2.376 min, m/z 381.2 (M+); chiral SFC (method G) RT 4.54 min (46.9% AP, 4.93 min (49.7% AP). 1H NMR (400 MHz, DMSO-d6) δ 7.30-7.40 (m, 5H), 7.07 (d, J=7 Hz, 2H) 6.94 (d, J=7), 2H; 5.08 (s, 2H), 4.10 (d, J=17.6, 1H), 3.97 (d, J=17.6, 1H), 3.77 (m, 2H), 3.43 (br s, 1H), 2.16 (m, 2H), 1.42 (s, 9H).

Workup

  1. additionafter the completion of the addition
  2. stirringthe mixture was stirred in the cold for a further 90 minutes
  3. customThe mixture was then partitioned between 200 mL brine and 200 mL DCM
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-81c7c9d483d049658174b155635db8d8
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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