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Potassium Carbonate → (4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

HRID 2045881
Notes
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Reaction equation

HRID 2045881 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:16][O:15][C@H:14]([C:17]([F:20])([F:19])[F:18])[C@H:13]1[CH2:12][S:11][C:10]([NH:21]C(=O)C1C=CC=CC=1)=[N:9]2.C([O-])([O-])=O.[K+].[K+]>CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:16][O:15][C@H:14]([C:17]([F:18])([F:19])[F:20])[C@H:13]1[CH2:12][S:11][C:10]([NH2:21])=[N:9]2
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 60168236N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Product 1

HCID 60168238(4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amineYield 97.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (250.2 g, 589.5 mmol) in methanol (1.25 L) was added K2CO3 (81.5 g, 590.0 mmol). The suspension was heated to 65° C. for 6 h. Upon cooling to ambient temperature, the solvent was evaporated under vacuum. To the resulting residue, was added 1.0 N aq NaOH (1.18 L) and THF (502 mL). The heterogeneous mixture was heated to 45° C. for 1 h. The mixture was cooled to ambient temperature, and EtOAc (1.38 L) was added. The aqueous layer was extracted with EtOAc (0.75 L). The organics were combined, washed with saturated aq. NaHCO3 (500 mL) and saturated aq. NaCl (500 mL). The organics were concentrated under vacuum to afford the title compound as a brown oil (184.1 g, 91.6% yield accounting for residual solvents). 1H NMR (500 MHz, DMSO) δ ppm 7.49-7.42 (m, 1H), 7.40-7.33 (m, 1H), 7.26-7.15 (m, 2H), 6.26 (s, 2H), 4.77-4.54 (m, 1H), 4.40 (d, J=8.0 Hz, 1H). 3.80 (dd, J=7.9, 2.3 Hz, 1H), 3.24-3.17 (m, 1H), 3.00 (dd, J=13.9, 3.2 Hz, 1H), 2.85 (dd, J=13.9, 3.9 Hz, 1H); 13C NMR (125 MHz, DMSO) δ ppm 159.75 (d, JCF=245.1 Hz), 149.51, 131.31 (d, JCF=3.9 Hz), 130.13 (d, JCF=8.8 Hz), 128.08 (d, JCF=10.4 Hz), 128.28 (q, JCF=282.1 Hz). 124.87 (d, JCF=3.0 Hz), 116.80 (d, J=23.8 Hz). 78.77, 76.80 (q, JCF=30.8 Hz), 66.31, 36.37, 23.27.

Workup

  1. temperatureUpon cooling to ambient temperature
  2. customthe solvent was evaporated under vacuum
  3. additionTo the resulting residue, was added 1.0 N aq NaOH (1.18 L) and THF (502 mL)
  4. temperatureThe heterogeneous mixture was heated to 45° C. for 1 h
  5. temperatureThe mixture was cooled to ambient temperature
  6. additionEtOAc (1.38 L) was added
  7. extractionThe aqueous layer was extracted with EtOAc (0.75 L)
  8. washwashed with saturated aq. NaHCO3 (500 mL) and saturated aq. NaCl (500 mL)
  9. concentrationThe organics were concentrated under vacuum

Sources & evidence

ORD record
ord-54e1cc251a164ebb976023c209cd85b2
Source dataset
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08592408B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes