Tributylamine → 1,1-Dimethylethyl N-[2-[[[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]carbonyl]amino]ethyl]carbamate

HRID 443320Notes

Reaction equation

HRID 443320 reaction equation
[CH2:1]([N:3]([CH2:18][CH3:19])[C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[C:9]([C:15]([OH:17])=O)[C:10](=[O:14])[O:11]2)=[CH:6][CH:5]=1)[CH3:2].C(N(CCCC)CCCC)CCC.ClC(OCC(C)C)=O.[NH2:41][CH2:42][CH2:43][NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48]>CN(C=O)C.CCOC(C)=O>[C:47]([O:46][C:45]([NH:44][CH2:43][CH2:42][NH:41][C:15]([C:9]1[C:10](=[O:14])[O:11][C:12]2[C:7]([CH:8]=1)=[CH:6][CH:5]=[C:4]([N:3]([CH2:1][CH3:2])[CH2:18][CH3:19])[CH:13]=2)=[O:17])=[O:51])([CH3:50])([CH3:49])[CH3:48]

Participants

7

Reactant 4

HCID 7622TributylamineHCID 62365Isobutyl chloroformateHCID 187201N-BOC-ethylenediamineHCID 6592947-Diethylaminocoumarin-3-carboxylic acid

Product 1

HCID 100241141,1-Dimethylethyl N-[2-[[[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]carbonyl]amino]ethyl]carbamateYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

--A solution of 7-diethylaminocoumarin-3-carboxylic acid 2 (1.15 g, 5 mmol) and tri-n-butylamine (1.38 g, 7.5 mmol) in dry DMF (50 ml) was cooled in an ice bath and treated with isobutyl chloroformate (0.715 g, 5.2 mmol). The solution was stirred in the ice bath for 0.5 h, then a solution of the amine 3 (0.8 g, 5 mmol) in dry DMF (5 ml) was added. The mixture was allowed to warm to room temp. and kept for 3 h, then diluted with EtOAc and washed thoroughly with water, dilute aq. HCl, aq. NaHCO3 and water, dried and evaporated. The residue gave a yellow solid after trituration with a little ether. A portion (400 mg) was purified by flash chromatography to give the amide 4 as yellow prisms (0.345 g), m.p. 157-158° C. after crystallisation from EtOAc-light petroleum The remaining material crystallised without chromatography to give a further portion of the product (0.55 g, total yield 45%) (Found. C, 62.6;. H, 7.3; N, 10.4. C21H29N3O5 requires C, 62.5; H, 7.2; N, 10.4%); δH 8.95 (1 H, t, J 5.5, NH), 8.68 (1 H, s, 4-H), 7.42 (1 H, d, Jortho 8.8, 5-H) , 6.64 (1 H, dd, Jmeta 2.3, 6-H), 6.49 (1 H, d, 8-H), 5.08 (1 H, br S, NH), 3.23-3.64 (8 H, m, 4×CH2), 1.44 (9 H, S, CMe3) and 1.24 (6 H, t, J7, 2×Me).

Workup

  1. temperatureto warm to room temp.
  2. washwashed thoroughly with water, dilute aq. HCl, aq. NaHCO3 and water
  3. customdried
  4. customevaporated
  5. customThe residue gave a yellow solid after trituration with a little ether
  6. customA portion (400 mg) was purified by flash chromatography

Sources & evidence

ORD record
ord-c77e396022494d63a257bddbcb7a9f37
Source dataset
uspto-grants-1999_04
Patent number
US05898069

Reaction notes

Loading…