Diisopropylethylamine → tert-Butyl[(1R,2R)-2-{[(4-bromo-5 ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

HRID 1842595Notes

Reaction equation

HRID 1842595 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]([OH:11])=O)[S:5][C:6]=1[CH2:7][CH3:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:39][C@H:40]1[C:45]([F:47])([F:46])[CH2:44][CH2:43][CH2:42][C@H:41]1[NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:51]([O:50][C:49](=[O:55])[NH:48][C@@H:41]1[CH2:42][CH2:43][CH2:44][C:45]([F:47])([F:46])[C@@H:40]1[NH:39][C:9]([C:4]1[S:5][C:6]([CH2:7][CH3:8])=[C:2]([Br:1])[CH:3]=1)=[O:11])([CH3:54])([CH3:52])[CH3:53]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 37663724-Bromo-5-ethylthiophene-2-carboxylic acidHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamate

Product 1

HCID 89750990tert-Butyl[(1R,2R)-2-{[(4-bromo-5 ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamateYield 78.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-5-ethylthiophene-2-carboxylic acid (1.00 g, 4.25 mmol) and BOP (5.64 g, 12.8 mmol) were dissolved in DMF (42.5 mL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (1.07 g, 4.25 mmol) and diisopropylethyl amine (1.11 mL, 6.38 mmol) and the reaction stirred at room temperature for 64 h. The reaction mixture was diluted with ethyl acetate and washed with water 3×. The organic layer was collected, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-50% EtOAc/Hex) to give the title compound (1.56 g, 3.34 mmol). LRMS (APCI) calc'd for (C18H25BrF2N2O3S) [M+H]+, 467.1; found 466.9. 1H NMR (CDCl3, 500 MHz) δ 7.32 (s, 1H), 6.28 (s, 1H), 4.90 (s, 1H), 4.54 (s, 1H), 4.29 (s, 1H), 2.81 (q, J=7.5, 2H), 2.22 (m, 1H), 1.88 (m, 1H), 1.81 (m, 1H), 1.69 (m, 1H), 1.59 (m, 1H), 1.46 (s, 9H), 1.41 (m, 1H), 1.28 (t, J=7.3, 3H)

Workup

  1. stirringthe reaction stirred at room temperature for 64 h
  2. washwashed with water 3×
  3. customThe organic layer was collected
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (0-50% EtOAc/Hex)

Sources & evidence

ORD record
ord-d8e259913f4749279045a11206275a8a
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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