Water → tert-Butyl (2-(5-chloropicolinoyl)-6-methoxyphenyl)carbamate

HRID 921265Notes

Reaction equation

HRID 921265 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].[Li]C(C)(C)C.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:29](OCC)=[O:30])=[N:27][CH:28]=1.O>CCOCC.CCOC(C)=O>[C:12]([O:11][C:10](=[O:16])[NH:9][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=1[C:29](=[O:30])[C:26]1[CH:25]=[CH:24][C:23]([Cl:22])=[CH:28][N:27]=1)([CH3:13])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 962WaterHCID 4935494tert-butyl N-(2-methoxyphenyl)carbamateHCID 15414989Ethyl 5-Chloropyridine-2-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 86713384tert-Butyl (2-(5-chloropicolinoyl)-6-methoxyphenyl)carbamateYield 57.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a cold (−23° C.), stirred solution of tert-butyl 2-methoxyphenylcarbamate (548 mg, 2.454 mmol) in ether (6 mL) under N2 was added t-BuLi (3.2 mL, 5.44 mmol). After stirring for 2.5 h, the reaction mixture was cooled to −78° C. To the reaction mixture was added a solution of ethyl 5-chloropicolinate (564.5 mg, 3.04 mmol) in ether (12 mL) dropwise via cannula over 5 min. The reaction mixture was stirred for 60 min, and then warmed to room temperature. After 1.5 h, to the reaction mixture was added H2O with vigorous stirring. The reaction mixture was diluted with EtOAc, and the organic phase was separated, washed with sat NaCl then dried (Na2SO4), filtered and concentrated to yield the product Intermediate A-29A (511.5 mg, 57.4% yield)) as a yellow solid: 1H NMR (400 MHz, chloroform-d) δ ppm 8.55 (1H, dd, J=2.3, 0.6 Hz), 8.08 (1H, dd, J=8.4, 0.7 Hz), 7.80 (1H, dd, J=8.4, 2.4 Hz), 7.16-7.25 (2H, m), 7.06 (1H, dd, J=7.5, 2.2 Hz), 6.90 (1H, s), 3.92 (3H, s), 1.28 (9H, s).

Workup

  1. stirringThe reaction mixture was stirred for 60 min
  2. temperaturewarmed to room temperature
  3. waitAfter 1.5 h
  4. customthe organic phase was separated
  5. washwashed with sat NaCl
  6. dry with materialthen dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield the product Intermediate A-29A (511.5 mg, 57.4% yield)) as a yellow solid

Sources & evidence

ORD record
ord-8c3d6cd24fdd4ab08499c8223dd680c4
Source dataset
uspto-grants-2016_03
Patent number
US09273014B2

Reaction notes

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