Water → 1,1-Dimethylethyl 9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 1514230Notes

Reaction equation

HRID 1514230 reaction equation
[OH:1][NH:2][C:3](=[NH:22])[C:4]1[C:14]2[O:13][CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[Cl:30][C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][C:39]=1[O:40][CH:41]([CH3:43])[CH3:42])[C:34](Cl)=O.O>CN(C)C=O>[Cl:30][C:31]1[CH:32]=[C:33]([C:34]2[O:1][N:2]=[C:3]([C:4]3[C:14]4[O:13][CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:9][C:8]=4[CH:7]=[CH:6][CH:5]=3)[N:22]=2)[CH:37]=[CH:38][C:39]=1[O:40][CH:41]([CH3:42])[CH3:43]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 21710470HCID 21710470, compoundHCID 178452412HCID 178452412, compound

Product 1

HCID 594034901,1-Dimethylethyl 9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 1,1-dimethylethyl 9-[(hydroxyamino)(imino)methyl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (Preparation 65) (32.9 g, 107 mmol) and triethylamine (17.9 ml, 128 mmol) in dry N,N-dimethylformamide (DMF) (200 ml) was cooled in ice/water under nitrogen. A solution of 3-chloro-4-[(1-methylethyl)oxy]benzoyl chloride (Preparation 102) (28.7 g, 123 mmol) in DMF (100 ml) was added over ca 20 minutes. When the addition was complete the mixture was allowed to warm to room temperature and stirred for 1 hour at room temperature, then at 120° C. for 3 hours. The mixture was allowed to cool and was poured into water (1 liter). The resulting solid was extracted into ethyl acetate (3×300 ml) and the extracts combined, washed with 1M hydrochloric acid (2×250 ml), then 1M sodium carbonate solution (3×250 ml), brine (250 ml), dried (sodium sulphate) and evaporated. The residue was purified by chromatography on silica. Eluting with a 10-40% gradient of ethyl acetate in isohexane to give the title compound as a crystalline solid (42.7 g) MS (ES): C25H2835ClN3O5 requires 485; found 486 [M+H]+.

Workup

  1. additionWhen the addition
  2. waitat 120° C. for 3 hours
  3. temperatureto cool
  4. extractionThe resulting solid was extracted into ethyl acetate (3×300 ml)
  5. washwashed with 1M hydrochloric acid (2×250 ml)
  6. dry with material1M sodium carbonate solution (3×250 ml), brine (250 ml), dried (sodium sulphate)
  7. customevaporated
  8. customThe residue was purified by chromatography on silica
  9. washEluting with a 10-40% gradient of ethyl acetate in isohexane

Sources & evidence

ORD record
ord-5ea24261b4194800be6cde8d304a8402
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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