Water → HCID 22914677, compound

HRID 1377705Notes

Reaction equation

HRID 1377705 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:21][OH:22])[CH:10]([C:23]([O:25][CH3:26])=[O:24])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.O>C1COCC1>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[CH2:21][O:22][C:28]2=[O:30])[CH:10]([C:23]([O:25][CH3:26])=[O:24])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 94429Triphosgene2×HCID 22914698HCID 22914698, compound

Product 1

HCID 22914677HCID 22914677, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 1-Boc-4-(2-hydroxymethylphenylamino)-3-piperidine carboxylate from Step 2 above (4.1 g, 11.3 mmol) was stirred in THF (40 mL) in an ice bath and treated with triphosgene (1.11 g, 3.74 mmol) followed by triethylamine (4.7 mL, 3.41 g, 33.7 mmol). The mixture was stirred at ambient temperature for 18 h, then treated with an additional 0.47 g of triphosgene and 1.9 mL of triethylamine, and stirred an additional 4.5 h. Water was added and the mixture was extracted with ethyl acetate. The combined ethyl acetate layers were washed with 2N HCl then with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered, and evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with CHCl3 followed by 1:99 MeOH:CHCl3. The combined product fractions were evaporated to dryness in vacuo to give methyl 1-Boc-4-(3,1-benzoxazin-2-one-1-yl)-3-piperidine carboxylate.

Workup

  1. stirringstirred an additional 4.5 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined ethyl acetate layers were washed with 2N HCl
  4. dry with materialwith saturated aqueous sodium bicarbonate, dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness in vacuo
  7. customThe residue was chromatographed on silica gel
  8. washeluted with CHCl3
  9. customThe combined product fractions were evaporated to dryness in vacuo

Sources & evidence

ORD record
ord-d488dd17d94a4a32957b4a345517f558
Source dataset
uspto-grants-1997_09
Patent number
US05665719

Reaction notes

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