tert-butyl N-(2-oxoethyl)carbamate → [6-(4-Methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-7-ylmethyl]-carbamic acid tert-butyl ester

HRID 724619Notes

Reaction equation

HRID 724619 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:18]=[CH:17][C:7]([CH2:8][NH:9][CH2:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)=[CH:6][CH:5]=1.O=[CH:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26]>C(O)CCC.C(OCC)(=O)C>[C:25]([O:24][C:23](=[O:29])[NH:22][CH2:21][CH:20]1[C:13]2[S:14][CH:15]=[CH:16][C:12]=2[CH2:11][CH2:10][N:9]1[CH2:8][C:7]1[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:18][CH:17]=1)([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 2

HCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 21878990(4-Methoxy-benzyl)-(2-thiophen-3-yl-ethyl)-amine Hydrochloride

Product 1

HCID 58746632[6-(4-Methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-7-ylmethyl]-carbamic acid tert-butyl esterYield 44.4%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4.11-A (5.6 g, 19.7 mmol) and t-butyl (2-oxoethyl)carbamate (12.6 g, 78.9 mmol) in butanol (118 mL) was heated to 140° C. for 16 h in a reaction vessel equiped with a Dean-Stark trap. The reaction mixture was cooled to 25° C. and diluted with ethyl acetate. The starting material 4.11-A precipitates as a white solid which was collected. The ethyl acetate filtrate was washed with saturated sodium bicarbonate (2×100 mL) and brine (100 mL), dried with Na2SO4, filtered, and concentrated to give a crude oil which was purified using flash column chromatography (100% hexane →30% EtOAc/hexane) to yield 4.11-B as an amber oil (3.4 g, 44%). 1H NMR (500 MHz, CDCl3): δ 7.26–7.25 (m, 2H), 7.18 (d, J=4.9 Hz, 1H), 6.88–6.85 (m, 2H), 6.81 (d, J=4.9 Hz, 1H), 5.05–5.00 (M, 1H), 3.81 (s, 3H), 3.80–3.78 (m, 1H), 3.72–3.64 (m, 2H), 3.57–3.53 (m, 1H), 3.20–3.15 (m, 1H), 3.15–3.08 (m, 1H), 2.90–2.78 (m, 2H), 2.48–2.45 (m, 1H), 1.42 (s, 9H); LCMS found for C21H29N2O3S (M+H)+: m/z=389.

Workup

  1. customequiped with a Dean-Stark trap
  2. customThe starting material 4.11-A precipitates as a white solid which
  3. customwas collected
  4. washThe ethyl acetate filtrate was washed with saturated sodium bicarbonate (2×100 mL) and brine (100 mL)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude oil which
  9. customwas purified

Sources & evidence

ORD record
ord-36063428dca548939bf96abcf7c84637
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

Loading…