tert-Butanol → Tert-butyl (5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamate

HRID 42494Notes

Reaction equation

HRID 42494 reaction equation
[C:1]([C:3]1[C:4]([CH3:14])=[CH:5][C:6](C(O)=O)=[N:7][C:8]=1[O:9][CH3:10])#[N:2].C([N:17]([CH2:20]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])=CC=1.[C:39]([OH:43])([CH3:42])([CH3:41])[CH3:40]>>[C:1]([C:3]1[C:4]([CH3:14])=[CH:5][C:6]([NH:17][C:20](=[O:29])[O:43][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:7][C:8]=1[O:9][CH3:10])#[N:2]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 674675275-Cyano-6-methoxy-4-methylpicolinic acid

Product 1

HCID 86677356Tert-butyl (5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamateYield 59.4%

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-cyano-6-methoxy-4-methylpicolinic acid (0.75 g, 3.90 mmol) in tert-butanol (25 mL) was added triethylamine (0.7 mL, 5.02 mmol). After the reaction became clear DPPA (1 mL, 4.64 mmol) was added dropwise over 5 minutes. The reaction was slowly heated to 100° C. and stirred for 4 hr. The reaction was cooled to RT and evaporated to dryness under vacuum. Purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 20% EtOAc in hexanes) to give, after trituration and filtration from hexanes, the product tert-butyl (5-cyano-6-methoxy-4-methylpyridin-2-yl)carbamate (0.61 g, 2.317 mmol, 59.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.44 (s, 1H), 3.91 (s, 3H), 2.40 (s, 3H), 1.48 (s, 9H). MS (ES)+m/e 264.0 [M+H]+.

Workup

  1. additionwas added dropwise over 5 minutes
  2. temperatureThe reaction was cooled to RT
  3. customevaporated to dryness under vacuum
  4. customPurified by silica gel chromatography (Analogix
  5. customSF25-60 g, 0 to 20% EtOAc in hexanes) to give
  6. filtrationafter trituration and filtration from hexanes

Sources & evidence

ORD record
ord-e50e1554872749b9ac0ecdf60ad262f8
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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