Hydrochloric Acid → HCID 58550974, compound

HRID 2204157Notes

Reaction equation

HRID 2204157 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]3([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[O:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=32)=[CH:4][CH:3]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[CH:40]([O:42]CCCC)=[CH2:41].C1(N(C)C2CCCCC2)CCCCC1.Cl>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[C:40]([C:2]1[N:10]2[C:5]([C:6]3([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:18][CH2:19]3)[O:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=32)=[CH:4][CH:3]=1)(=[O:42])[CH3:41]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 24210N-Methyl dicyclohexylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 58551010HCID 58551010, compound

Product 1

HCID 58550974HCID 58550974, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 1′-bromospiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate (1.10 g, 2.60 mmol) and Pd2(dba)3.OCHCl3 (543 mg, 0.525 mmol) in 1,4-dioxane (4.4 mL) was added tri-tert-butylphosphane (360 μL, 1.31 mmol), 1-vinyloxybutane (3.55 mL, 26.2 mmol) and N-cyclohexyl-N-methyl-cyclohexanamine (843 μL, 3.94 mmol). The mixture was heated at 80° C. for 5 hours. The mixture was cooled to room temperature before 1N HCl (3 mL) was added and the mixture was stirred for 1 hour. The mixture was poured into water and was extracted with ethyl acetate (4×). The organics were combined, washed with water (2×), brine and evaporated. The residue was purified by column chromatography (0-20% ethyl acetate in hexanes) to give tert-butyl 1′-acetylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate (610 mg, 61%) as a yellow solid. ESI-MS m/z calc. 382.2, found 383.1 (M+1)+; Retention time: 1.97 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.52 (dd, J=8.1, 1.3 Hz, 1H), 7.35 (d, J=4.1 Hz, 1H), 7.24-7.12 (m, J=9.4, 8.0, 1.6 Hz, 2H), 7.08-6.98 (m, 1H), 6.35 (d, J=4.1 Hz, 1H), 3.88 (d br, J=11.3 Hz, 2H), 3.13 (s br, 2H), 2.49 (s, 3H), 1.92-1.76 (m, 4H), 1.41 (s, 9H).

Workup

  1. additionwas added
  2. extractionwas extracted with ethyl acetate (4×)
  3. washwashed with water (2×), brine
  4. customevaporated
  5. customThe residue was purified by column chromatography (0-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d053878feab340138c593d1732af475d
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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