Acetic Acid → HCID 54188068, compound

HRID 1637085Notes

Reaction equation

HRID 1637085 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:15])[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(O)(=O)C.[C:20]([O:24][C:25]([NH:27][C@@H:28]1[CH2:32][CH2:31][NH:30][CH2:29]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([BH3-])#N.[Na+]>CO.CC(O)C.C(OCC)(=O)C>[C:20]([O:24][C:25]([NH:27][C@@H:28]1[CH2:32][CH2:31][N:30]([CH:11]2[CH2:12][CH2:13][C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)([OH:15])[CH2:9][CH2:10]2)[CH2:29]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 223953644-(4-Fluorophenyl)-4-hydroxycyclohexan-1-one

Product 1

HCID 54188068HCID 54188068, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 22055037Isopropanol ethyl acetateSolvent

Procedure

To a solution of 4-(4-Fluorophenyl)-4-hydroxy-cyclohexanone (2.0 g, 9.6 mmol) and acetic acid (2.6 ml, 48 mmol) in methanol (60 ml) was added (3R)-(+)-3-(tert-butoxycarbonylamino) pyrrolidine (2.6 g, 14.4 mmol). After stirring for 2 hours at room temperature, sodium cyanoborohydride (1M in tetrahydrofuran, 14.4 ml, 14.4 mmol) was added dropwise. The reaction mixture was stirred for 45 minutes, concentrated, diluted with 10% potassium hydrogen sulfate and extracted twice with ether. The aqueous solution was basified with 1N sodium hydroxide and extracted with ethyl acetate three times. Washing with brine, drying and solvent evaporation gave an oil. Flash chromatography (silica gel, 2-propanol-ethyl acetate, 4:96 increasing to 8:92) gave 4-(3-(3R)-tert-Butoxycarbonylamino-pyrrolidin-1-yl)-1-(4-fluorophenyl)-cyclohexanol (2.0 g, 56%); 1H NMR (CDCl3)δ 7.46(m, 2H), 7.02 (m, 2H), 4.89 (m, 1H), 4.18 (m, 1H), 2.94 (m, 1H), 2.71 (m, 2H), 2.42 (m, 1H), 2.26 (m, 1H), 2.13 (m, 1H), 1.83 (m, 9H), 1.63 (m, 1H), 1.44 (s, 9H),

Workup

  1. stirringThe reaction mixture was stirred for 45 minutes
  2. concentrationconcentrated
  3. additiondiluted with 10% potassium hydrogen sulfate
  4. extractionextracted twice with ether
  5. extractionextracted with ethyl acetate three times
  6. washWashing with brine
  7. customdrying
  8. customsolvent evaporation
  9. customgave an oil

Sources & evidence

ORD record
ord-683fb28eec934c19a8f7fb53f53c755b
Source dataset
uspto-grants-2000_03
Patent number
US06037354

Reaction notes

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