Trimethyl orthoformate → tert-butyl (4S,7S,10aS)-7-(1,3,4-oxadiazol-2-yl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

HRID 529482Notes

Reaction equation

HRID 529482 reaction equation
[NH:1]([C:3]([C@H:5]1[N:15]2[C@@H:9]([S:10][CH2:11][CH2:12][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:14]2=[O:16])[CH2:8][CH2:7][CH2:6]1)=[O:4])[NH2:2].[CH3:25]OC(OC)OC>>[O:4]1[CH:25]=[N:2][N:1]=[C:3]1[C@H:5]1[N:15]2[C@@H:9]([S:10][CH2:11][CH2:12][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:23])[CH3:22])[C:14]2=[O:16])[CH2:8][CH2:7][CH2:6]1

Participants

3

Reactant 2

HCID 9005Trimethyl orthoformateHCID 68311186tert-butyl (4S,7S,10aS)-7-(hydrazinecarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

Product 1

HCID 68311017tert-butyl (4S,7S,10aS)-7-(1,3,4-oxadiazol-2-yl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 74.3%

Conditions

Temperature
70 °C

Procedure

To a round bottom flask was added tert-butyl (4S,7S,10aS)-7-(hydrazinecarbonyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (0.13 g, 0.35 mmol) and trimethoxymethane (2.50 mL, 22.9 mmol). The reaction was heated at 70° C. for 5 hr. and then at 95° C. for 18 hr. The reaction was concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-60% EtOAc/Hex to give tert-butyl (4S,7S,10aS)-7-(1,3,4-oxadiazol-2-yl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (94 mg, 0.26 mmol, 73% yield) as a white solid. Anal. Calcd. for C16H24N4O4S m/z 368.4. found: 369.1 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customThe residue was purified
  3. washeluting with a gradient of 0-60% EtOAc/Hex

Sources & evidence

ORD record
ord-505560a54a7444e0b4172b42a971b70e
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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