Trifluoroacetic acid → HCID 10841069, compound

HRID 1068079Notes

Reaction equation

HRID 1068079 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([C:34]([O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35])[CH2:18][C@H:19]([OH:33])[CH2:20][CH2:21][NH:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C:10]([OH:12])=[O:11].[O:44]1[CH:49]=[CH:48][CH2:47][CH2:46][CH2:45]1>C(Cl)(Cl)Cl>[NH2:8][C@@H:9]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([C:34]([O:36][CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)=[O:35])[CH2:18][C@H:19]([O:33][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)[CH2:20][CH2:21][NH:22][C:23]([O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:24])[C:10]([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 80803,4-dihydro-2H-pyran2×HCID 10744014HCID 10744014, compound

Product 1

HCID 10841069HCID 10841069, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Trifluoroacetic acid (164 mg, 1.44 mmol) was added to a solution of 17a (360 mg, 0.72 mmol) in CHCl3 (7 mL). The solution was concentrated in vacuo. The resultant oil was dissolved in CH2Cl2 (20 mL), and 3,4-dihydro-2H-pyran (69 mg, 75 μL, 0.83 mmol) was added at room temperature. The reaction progress was monitored by TLC, and six additional portions of 3,4-dihydro-2H-pyran (69 mg each) were added over the next 31 hours. The reaction mixture was stirred for an additional 16 hours and concentrated in vacuo. The oil was dissolved in water (4 mL) and methanol (8 mL), then adjusted to pH 7 with saturated NaHCO3 solution. The solution was concentrated, and the crude oil was purified by chromatography on a C-18 column (30% acetone/water, followed by 55% acetone/water) to give 18a (219 mg, 52%) as a colorless oil: 1H NMR δ 1.20-1.98 (m, 14H), 3.06-3.56 (m, 8H), 3.68-4.02 (m, 2H), 4.33-4.62 (m, 1H), 5.06 (s, 2H), 5.11 (s, 2H), 7.24-7.36 (m, 10H); 13C NMR δ 20.7, 21.1, 21.7, 23.6, 26.3, 26.5, 32.0, 32.5, 34.2, 38.1, 38.5, 52.0, 56.2, 64.2, 65.2, 67.3, 68.3, 74.9, 100.1, 101.6, 128.79, 128.96, 129.02, 129.10, 129.20, 129.47, 129.56, 129.62, 138.3, 138.5, 158.0, 158.7, 174.8; HRMS m/z calcd for C31H43N3NaO8 608.2948, found 608.2954.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. dissolutionThe resultant oil was dissolved in CH2Cl2 (20 mL)
  3. additionwere added over the next 31 hours
  4. concentrationconcentrated in vacuo
  5. dissolutionThe oil was dissolved in water (4 mL)
  6. concentrationThe solution was concentrated
  7. customthe crude oil was purified by chromatography on a C-18 column (30% acetone/water, followed by 55% acetone/water)

Sources & evidence

ORD record
ord-c540aa98220f4302ac2e3a4b35c83382
Source dataset
uspto-grants-2001_06
Patent number
US06248866B1

Reaction notes

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