Triethylamine → Trifluoroacetic acid

HRID 1184627Notes

Reaction equation

HRID 1184627 reaction equation
[F:1][CH:2]([F:6])[C:3]([OH:5])=[O:4].ClC(OCC(C)C)=O.C(N(CC)CC)C.[NH2:22][CH:23]([C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=1)[C:24]([N:26]1[CH2:31][CH2:30][N:29]2[CH2:32][C@H:33]([O:35][C:36]3[CH:41]=[N:40][C:39]([CH:42]4[CH2:44][CH2:43]4)=[CH:38][N:37]=3)[CH2:34][C@H:28]2[CH2:27]1)=[O:25]>ClCCl>[CH:42]1([C:39]2[N:40]=[CH:41][C:36]([O:35][C@H:33]3[CH2:32][N:29]4[CH2:30][CH2:31][N:26]([C:24](=[O:25])[CH:23]([NH:22][C:3](=[O:4])[CH:2]([F:6])[F:1])[C:45]5[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=5)[CH2:27][C@@H:28]4[CH2:34]3)=[N:37][CH:38]=2)[CH2:43][CH2:44]1.[F:1][C:2]([F:52])([F:6])[C:3]([OH:5])=[O:4]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 9788Difluoroacetic acidHCID 62365Isobutyl chloroformateHCID 86680533HCID 86680533, compound

Product 2

HCID 6422Trifluoroacetic acidYield 458.4%HCID 86680544HCID 86680544, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2,2-difluoroacetic acid (0.0083 mL, 0.131 mmol) in anhydrous dichloromethane (1 mL) at 0° C. under N2 was treated with isobutyl chloroformate (0.014 mL, 0.105 mmol) and triethylamine (0.025 mL). The resulting mixture was stirred at 0° C. for 40 minutes, and the product from Example 200 (50 mg, 0.088 mmol) was added, followed by triethylamine (0.060 mL). The resulting mixture was stirred at room temperature for 90 minutes and partitioned between water and dichloromethane (3×). The combined organic layers were concentrated in vacuo, and the crude product was purified by column chromatography on C18 silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid). The title compound was obtained as a trifluoroacetic acid salt (23 mg). 1H NMR (300 MHz, CDCl3) δ ppm 0.89-1.06 (m, 4 H) 1.92-4.89 (m, 14 H) 5.38-5.56 (m, 1 H) 5.70-5.89 (m, 1 H) 7.46-7.76 (m, 4 H) 7.86-8.10 (m, 2 H); MS (ESI) m/z 540 (M+H)+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 90 minutes
  2. custompartitioned between water and dichloromethane (3×)
  3. concentrationThe combined organic layers were concentrated in vacuo
  4. customthe crude product was purified by column chromatography on C18 silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-3450916e5e864688aca9322fe3d42c55
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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