Triethylamine → HCID 117856674, compound

HRID 1497283Notes

Reaction equation

HRID 1497283 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@H:14]2[NH:15][C:16](=O)[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][F:20])[C@H:10]1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.C[O+](C)C.Cl.[NH:39]1[CH2:42][CH2:41][CH2:40]1.CCN(CC)CC>C(Cl)Cl.C1COCC1.C([O-])(O)=O.[Na+]>[N:39]1([C:16]2[O:17][C@H:13]3[CH2:12][C@H:11]([CH2:19][F:20])[C@@H:10]([O:21][CH2:22][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[C@H:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[C@H:14]3[N:15]=2)[CH2:42][CH2:41][CH2:40]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 12308726Azetidine hydrochlorideHCID 71152401HCID 71152401, compound

Product 1

HCID 117856674HCID 117856674, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (3aS,4R,5R,6S,7aS)-4,5-bis(benzyloxy)-6-(fluoromethyl)hexahydrobenzo[d]oxazol-2(3H)-one (193 mg, 0.503 mmol) in DCM (4 mL) at room temperature was added 4 A molecular sieves (130 mg) followed by trimethyloxonium tetrafluoroborate (372 mg, 2.52 mmol). The mixture was stirred at room temperature under N2 for 24 h. Azetidine hydrochloride (236 mg, 2.52 mmol) and a solution of Et3N (279 mg) in THF (2.0 mL) was added. The mixture was stirred at room temperature for another 48 h. The reaction was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with DCM (2×15 mL). The extracts were dried with Na2SO4 and the solvents were evaporated to give the crude product. This was purified by silica gel column, eluted with 2%-5% 2 M NH3 MeOH solution in DCM to yield (3aS,4R,5R,6S,7aS)-2-(azetidin-1-yl)-4,5-bis(benzyloxy)-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole as a white solid (80.0 mg, 38%). MS m/z 425.2 (M+1, 100%); 1H NMR (500 MHz, CDCl3) δ 7.28-7.36 (m, 10H), 4.93-4.96 (m, 1H), 4.77 (d, J=11.7 Hz, 1H), 4.71 (d, J=11.1 Hz, 1H), 4.65 (d, J=11.7 Hz, 1H), 4.54 (dd, J=9.0 Hz, 5.0 Hz, 1H), 4.49 (d, J=11.2 Hz, 1H), 4.43-4.46 (m, 1H), 4.43 (d, J=11.1 Hz, 1H), 4.34 (dd, J=9.0 Hz, 4.7 Hz, 1H), 4.20 (dd, J=8.3 Hz, 3.7 Hz, 1H), 3.88-3.99 (m, 4H), 3.86 (t, J=4.3 Hz, 1H), 3.53 (t, J=5.7 Hz, 1H), 2.09-2.19 (m, 4H), 1.81-1.87 (m, 1H).

Workup

  1. stirringThe mixture was stirred at room temperature for another 48 h
  2. extractionextracted with DCM (2×15 mL)
  3. dry with materialThe extracts were dried with Na2SO4
  4. customthe solvents were evaporated
  5. customto give the crude product
  6. customThis was purified by silica gel column
  7. washeluted with 2%-5% 2 M NH3 MeOH solution in DCM

Sources & evidence

ORD record
ord-3b7f74a553b84d1393f484b7ae089231
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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