1,2-Dichloroethane → (4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone

HRID 1908153Notes

Reaction equation

HRID 1908153 reaction equation
[CH:1]1[N:9]2[C:4]([C:5]3([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[O:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)=[CH:3][CH:2]=1.[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][C:21]=1[S:29]([CH3:32])(=[O:31])=[O:30].C(N(CC)CC)C.C(Cl)CCl>ClCCl>[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([N:16]2[CH2:17][CH2:18][C:5]3([C:4]4=[CH:3][CH:2]=[CH:1][N:9]4[C:8]4[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=4[O:6]3)[CH2:14][CH2:15]2)=[O:25])=[CH:22][C:21]=1[S:29]([CH3:32])(=[O:30])=[O:31]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 106803154-Fluoro-3-(methylsulphonyl)benzoic acidHCID 58550727Spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]

Product 1

HCID 58551140(4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanoneYield 54.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (257 mg, 0.928 mmol), 4-fluoro-3-methylsulfonyl-benzoic acid (203 mg, 0.928 mmol), triethylamine (518 μL, 3.71 mmol), and EDC (196 mg, 1.02 mmol) were combined in dichloromethane (10 mL) and the reaction mixture was stirred at room temperature for 4 d. The reaction mixture was washed three times with a 1M solution of hydrochloric acid, followed by three washes with a saturated aqueous solution of sodium bicarbonate, followed by three washes of a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to yield the crude product. The crude material was purified column chromatography utilizing a gradient of 0-75% ethyl acetate in hexanes to yield (4-fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone (222 mg, 54%) as a colorless oil. ESI-MS m/z calc. 440.1. found 441.1 (M+1)+; Retention time: 1.51 minutes (3 min run).

Workup

  1. washThe reaction mixture was washed three times with a 1M solution of hydrochloric acid
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customto yield the crude product
  6. customThe crude material was purified column chromatography

Sources & evidence

ORD record
ord-0c8bbe6cbd5c44f2bd88acbc5c0f3eb1
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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