Dichloroacetic Acid → HCID 58550801, compound

HRID 1907990Notes

Reaction equation

HRID 1907990 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[OH:13])[CH:3]=1.[O:14]=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.ClC(Cl)C(O)=O>ClCCl>[CH3:1][C:2]1[CH:6]=[CH:5][N:4]2[C:3]=1[C:15]1([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)[O:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]2=1.[CH3:1][C:2]1[CH:6]=[C:5]2[N:4]([CH:3]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:14][C:15]12[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]1

Participants

6

Reactant 3

HCID 6597Dichloroacetic AcidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 227234482-(3-Methyl-1-pyrrolyl)phenol

Product 2

HCID 58550801HCID 58550801, compoundHCID 58551567HCID 58551567, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-(3-methylpyrrol-1-yl)phenol (2.0 g, 12 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.5 g, 13 mmol) in dichloromethane (36 mL) under N2 was added, dropwise at 0° C., dichloroacetic acid (1.9 mL, 23 mmol) over 5 min. The mixture was stirred at that temperature for 2 h then held at 5° C. overnight. The mixture was washed with water (10 mL), 1M NaOH (20 mL) and brine (10 mL), dried over MgSO4 and purified by column chromatography (0-30% EtOAc/hexane) to give a mixture of product isomers (˜2.7 g, 68%, 2:1 ratio by NMR). The mixture was subjected to SFC separation using ChiralPak OD-H (30% MeOH w/0.1% DEA, 70% CO2) to give tert-butyl 3-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-carboxylate as the first eluting fraction (1.0 g, 37%) and tert-butyl 2′-methylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate as the second eluting fraction (0.40 g, 30%).

Workup

  1. waitthen held at 5° C. overnight
  2. washThe mixture was washed with water (10 mL), 1M NaOH (20 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. custompurified by column chromatography (0-30% EtOAc/hexane)
  5. customto give
  6. additiona mixture of product isomers (˜2.7 g, 68%, 2:1 ratio by NMR)
  7. customThe mixture was subjected to SFC separation

Sources & evidence

ORD record
ord-53f0c33e1f624a4d9aef1d13945adfd6
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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