Di-tert-butyl dicarbonate → HCID 24757051, compound

HRID 390751Notes

Reaction equation

HRID 390751 reaction equation
[F:1][C:2]([F:46])([F:45])[C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C@H:25]([N:29]1[CH2:34][CH2:33][CH:32](C(O)=O)[CH2:31][CH2:30]1)[CH:26]([CH3:28])[CH3:27])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[C:62](=[O:65])([O-])[O-].[NH4+:66].[NH4+].C(=O)(O)[O-].[Na+]>C1COCC1.N1C=CC=CC=1>[F:1][C:2]([F:46])([F:45])[C:3]1[CH:4]=[C:5]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:40]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C@H:25]([N:29]1[CH2:34][CH2:33][CH:32]([C:62]([NH2:66])=[O:65])[CH2:31][CH2:30]1)[CH:26]([CH3:28])[CH3:27])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

7

Reactant 4

HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 517111Ammonium CarbonateHCID 24756629HCID 24756629, compound

Product 1

HCID 24757051HCID 24757051, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-1-{-1-[2-({[3,5-bis(trifluoromethyl)benzyl](2-methyl-2H-tetrazol-5-yl)amino}methyl)-4-(trifluoromethyl)phenyl]-2-methylpropyl}piperidine-4-carboxylic acid (0.510 g, 0.76 mMol) in THF (5 mL) was added ditert-butyl dicarbonate (0.21 g, 0.99 mMol) and ammonium carbonate (0.078 g, 0.99 mMol) at 0° C. To this solution was added pyridine (0.037 mL) and the mixture was stirred overnight at room temperature. The reaction mixture was poured into saturated sodium bicarbonate and extracted with ethyl acetate. The extracts were washed with saturated solution of sodium hydrogen sulfate and brine. The organic extract was dried and purified by flash chromatography to afford the product (0.314 g., 65%) 1HNMR (400 MHz. CDCl3) δ 7.80 (s, 1H), 7.60 (d, 2H), 7.50 (m, 1H), (7.20, m, 1H), 7.25 (d, 1H), 5.20 (m, 2H), 4.90 (d, 1H), 4.70 (dd, 2H), 4.50 (dd, 1H, 4.20 (s, 3H), 3.60 (d, 1H), 3.0 (m, 1H), 2.80 (m, 1H), 2.20 (m, 1H), 1.80 (m, 2H), 1.70 (m, 4H), 0.8 (d, 3H), 0.6 (d, 3H). MS (ES+) Calc 665.60, Found 666.7 (M+1)

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extracts were washed with saturated solution of sodium hydrogen sulfate and brine
  3. extractionThe organic extract
  4. customwas dried
  5. custompurified by flash chromatography
  6. customto afford the product (0.314 g., 65%) 1HNMR (400 MHz. CDCl3) δ 7.80 (s, 1H), 7.60 (d, 2H), 7.50 (m, 1H), (7.20, m, 1H), 7.25 (d, 1H), 5.20 (m, 2H), 4.90 (d, 1H), 4.70 (dd, 2H), 4.50 (dd, 1H, 4.20 (s, 3H), 3.60 (d, 1H), 3.0 (m, 1H), 2.80 (m, 1H), 2.20 (m, 1H), 1.80 (m, 2H), 1.70 (m, 4H), 0.8 (d, 3H), 0.6 (d, 3H)

Sources & evidence

ORD record
ord-81a0243135334f268cd18ac649df7aa9
Source dataset
uspto-grants-2013_02
Patent number
US08383660B2

Reaction notes

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