2-Aminophenol → HCID 117903196, compound

HRID 520774Notes

Reaction equation

HRID 520774 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([NH:12][P:13]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:14])[CH2:9][CH:10]=[CH2:11].NC1C=CC=CC=1O.[O-2].[Al+3].[O-2].[O-2].[Al+3].[CH2:40]([N:44](CCCC)[C:45]1C=C[C:48](/C=N/P(C2C=CC=CC=2)(C2C=CC=CC=2)=O)=[CH:47][CH:46]=1)[CH2:41][CH2:42][CH3:43]>ClCCl.C(OCC)C.CO>[CH2:40]([N:44]([CH2:45][CH2:46][CH2:47][CH3:48])[C:6]1[CH:5]=[CH:4][C:3]([C@H:8]([NH:12][P:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:14])[CH2:9][CH:10]=[CH2:11])=[CH:2][CH:7]=1)[CH2:41][CH2:42][CH3:43]

Participants

7

Reactant 4

HCID 58012-Aminophenol2×HCID 9989226AluminaHCID 117902212HCID 117902212, compoundHCID 117904054HCID 117904054, compound

Product 1

HCID 117903196HCID 117903196, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

The title compound is synthesized analogously to 4b except for the following changes: 1) 2.5 mol % aminophenol 2g (instead of 3 mol % 2g) 2) 1.5 equiv. MeOH (instead of 2.5 equiv.). 3) Reaction time is six h. 4) After NaIO4 workup (see representative procedure above), the unpurified mixture is treated for 12 h while allowing it to stir with ˜1 g basic aluminum oxide in 4 mL dichloromethane:diethyl ether (1:1) to hydrolyze unreacted 3j, after which the aluminum oxide is filtered off and washed with dichloromethane and ethyl acetate (20 mL). The product is purified as described for 4b, affording 4j (44.2 mg, 0.0931 mmol, 93% yield) as a white solid. M.p.=83-84° C. IR (neat): 3154 (w, br), 3071 (w), 2955 (m), 2930 (m), 2870 (m), 1614 (m), 1519 (m), 1455 (m), 1436 (m), 1368 (w), 1283 (w), 1181 (s), 1107 (s), 1066 (m), 925 (m), 900 (m), 752 (w), 722 (s), 693 (s), 553 (s), 521 (s) cm−1; 1H NMR (400 MHz, CDCl3): δ 7.89-7.79 (4H, m), 7.49-7.32 (6H, m), 7.03 (2H, d, J=8.8 Hz), 6.54 (2H, d, J=8.8 Hz), 5.63 (1H, app ddt, J=17.2, 10.0, 7.2 Hz), 5.10-4.99 (2H, m), 4.26-4.19 (1H, m), 3.23 (4H, app dd, J=7.8, 7.2 Hz), 3.26-3.21 (1H, m, overlapping with the dd at 3.23), 2.75-2.58 (2H, m), 1.59-1.52 (4H, m), 1.40-1.30 (4H, app sextet, J=7.6 Hz), 0.96 (6H, t, J=7.6 Hz); 13C NMR (100 MHz, CDCl3): δ 147.3, 134.6, 133.6 (d, J=127.0 Hz), 132.6 (d, J=9.5 Hz), 132.4 (d, J=130.0 Hz), 131.9 (d, J=9.3 Hz), 131.7 (d, J=2.7 Hz), 131.6 (d, J=2.7 Hz), 129.2 (d, J=6.3 Hz), 128.4 (d, J=12.3 Hz), 128.3 (d, J=12.4 Hz), 127.6, 118.1, 111.5, 54.3, 50.9, 43.5 (d, J=3.7 Hz), 29.5, 20.4, 14.1; HRMS Calcd for C30H40N2OP [M+H]+: 475.28782. Found: 475.28783. [α]20D=+61.6 (c=1.33, CHCl3) for a 92:8 er sample. The enantiomeric purity of this compound was determined by HPLC analysis in comparison with authentic racemic material (Chiracel OD-H, 92:8 hexanes:i-PrOH, 0.5 mL/min, 220 nm): tR of 4j: 12 min (major) and 14 min (minor).

Workup

  1. custom3) Reaction time
  2. filtrationafter which the aluminum oxide is filtered off
  3. washwashed with dichloromethane and ethyl acetate (20 mL)
  4. customThe product is purified

Sources & evidence

ORD record
ord-a03d9fb48e934eeb930d0107f9b7fd4f
Source dataset
uspto-grants-2016_05
Patent number
US09328061B2

Reaction notes

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