tert-Butanol → 2-(N-Boc-amino)-3-phenyl-thiophene

HRID 530687Notes

Reaction equation

HRID 530687 reaction equation
[C:1]1([C:7]2[CH:11]=[CH:10][S:9][C:8]=2C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC[N:17]([CH2:20]C)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])C=CC=CC=1.[C:39]([OH:43])([CH3:42])([CH3:41])[CH3:40]>>[C:39]([O:43][C:20](=[O:29])[NH:17][C:8]1[S:9][CH:10]=[CH:11][C:7]=1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([CH3:42])([CH3:41])[CH3:40]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 25176253-phenylthiophene-2-carboxylic Acid

Product 1

HCID 589118012-(N-Boc-amino)-3-phenyl-thiopheneYield 45%

Conditions

Temperature
85 °C

Procedure

3-Phenyl-thiophene-2-carboxylic acid (200 mg, 979 μmol), NEt3 (99.1 mg, 136 μL, 979 μmol) and diphenylphosphoryl azide (275 mg, 215 μL, 999 μmol) were dissolved in tert-BuOH. The solution was stirred at 85° C. for 5 h followed by RT overnight. The formed suspension was filtered and the filter cake was washed with a small amount of tert-BuOH. The filtrate was diluted with EtOAc, washed with H2O and brine. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (0% to 18% EtOAc in n-heptane) to give the title compound as a yellow solid (0.122 g, 45%). MS (ESI): m/z=276.2 [M+H]+.

Workup

  1. waitfollowed by RT overnight
  2. filtrationThe formed suspension was filtered
  3. washthe filter cake was washed with a small amount of tert-BuOH
  4. additionThe filtrate was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialThe organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (0% to 18% EtOAc in n-heptane)

Sources & evidence

ORD record
ord-896c6274f1ac44089b8052396d25c67c
Source dataset
uspto-grants-2016_05
Patent number
US09353102B2

Reaction notes

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